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Human epidermal growth factor receptor-2 (HER2) is overexpressed in various solid tumor types, acting as an established therapeutic target. Over the last three decades, the fast-paced development of diverse HER2-targeted agents, notably marked by the introduction of the antibody-drug conjugate (ADC), yielding substantial improvements in survival rates. However, resistance to anti-HER2 treatments continues to pose formidable challenges. The complex structure and dynamic dimerization properties of HER2 create significant hurdles in the development of novel targeted therapeutics. In this review, we synthesize the latest insights into the structural intricacies of HER2 and present an unprecedented overview of the epitope characteristics of HER2-targeted antibodies and their derivatives. Furthermore, we delve into the correlation between anti-HER2 antibody binding epitopes and their respective functions, with a particular focus on their efficacy against resistant tumors. In addition, we highlight the potential of emerging anti-HER2 agents that target specific sites or non-overlapping epitopes, poised to transform the therapeutic landscape for HER2-positive tumors in the foreseeable future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The prognostic effects of the Patient-Generated Subjective Global Assessment (PG-SGA) criteria in cancer survivors have been observed but require validation in clinical practice. This study was designed to evaluate the prognostic effects of baseline and longitudinal changes in PG-SGA scores on all-cause mortality among Chinese cancer patients in a real-world setting., Methods: Study patients were selected from one representative tertiary hospital in West China. Kaplan-Meier curves and Cox regression analyses were used to estimate the prognostic effect of baseline and dynamic changes in PG-SGA scores on the all-cause mortality of cancer patients. Receiver operating characteristic curves and a concordance index were used to evaluate the predictive accuracy of PG-SGA criteria., Results: A total of 1415 cancer patients were included in this study, with a mean age of 46 years old. Cox regression analysis showed that baseline malnourished status was significantly associated with the survival of cancer patients (PG-SGA 4-8: hazard ratio [HR] = 1.46, 95% confidence interval [CI]: 1.09-1.96, P = 0.012; PG-SGA ≥9: HR = 1.78, 95% CI: 1.34-2.37, P < 0.001). Cancer patients with longitudinal increased PG-SGA scores (>2 points) were observed to have high risks for mortality (HR = 1.69, 95% CI: 1.04-2.74, P = 0.033). Compared with longitudinal changes in PG-SGA scores, baseline malnourished status showed higher predictive power in identifying the risk subgroup (concordance index: 0.646 vs. 0.586). Sensitivity analyses supported the main findings., Conclusions: This study highlights the prognostic value of baseline and dynamic changes in PG-SGA scores for cancer patients, which can help improve their outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies., Methods: AYA cancer, defined as cancer occurring in individuals aged 15-39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC)., Results: In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: - 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: - 1.64), but the decline slowed from 2012 (AAPC: - 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI., Conclusion: AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers., (© 2024. The Author(s).)

The fragmentation patterns of cell-free DNA (cfDNA) in plasma can potentially be utilized as diagnostic biomarkers in liquid biopsy. However, our knowledge of this biological process and the information encoded in fragmentation patterns remains preliminary. Here, we investigated the cfDNA fragmentomic characteristics against nucleosome positioning patterns in hematopoietic cells. cfDNA molecules with ends located within nucleosomes were relatively shorter with altered end motif patterns, demonstrating the feasibility of enriching tumor-derived cfDNA in patients with cancer through the selection of molecules possessing such ends. We then developed three cfDNA fragmentomic metrics after end selection, which showed significant alterations in patients with cancer and enabled cancer diagnosis. By incorporating machine learning, we further built high-performance diagnostic models, which achieved an overall area under the curve of 0.95 and 85.1% sensitivity at 95% specificity. Hence, our investigations explored the end characteristics of cfDNA fragmentomics and their merits in building accurate and sensitive cancer diagnostic models., Competing Interests: Declaration of interests Y.A., J.J., and K.S. have filed patent applications based on the method developed in this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Obesity is as an important risk factor for chronic diseases. Metabolically healthy obesity (MHO) is considered a benign state. The association between metabolic health and obesity categories and cancer risk remains unclear. This study aimed to investigate the relationship between metabolic health status combined with obesity phenotypes and the risk of cancer., Methods: Data from 91,834 participants in the Kailuan cohort were analyzed, excluding individuals with a body mass index (BMI) < 18.5 kg/m² and those with a history of cancer. Obesity phenotypes were classified based on BMI and waist circumference (WC) combined with metabolic health status, resulting in six phenotypes. Cox proportional hazard regression models were used to assess the association between metabolic health and obesity phenotypes with cancer risk and all-cause mortality., Results: The prevalence of metabolically healthy obesity and metabolically unhealthy obesity defined by BMI was 6.86% and 12.18%, while that defined by WC was 20.79% and 25.76%, respectively. Compared to metabolically healthy participants, individuals with an unhealthy metabolic status had a significantly higher risk of cancer (HR, 1.09; 95% CI, 1.03-1.15; p=0.004). The hazard ratios for cancer were 1.19, 1.23, 1.20, and 1.55 for individuals with one, two, three, and four metabolic disorders, respectively. Among those classified as metabolically unhealthy, both overweight and obesity were associated with a protective effect on cancer risk (HR, 0.88; 95% CI, 0.80-0.96; p=0.006 for overweight; HR, 0.87; 95% CI, 0.78-0.97; p=0.010 for obesity). However, abdominal obesity significantly increased cancer risk in both metabolically healthy and unhealthy participants. In subgroup analysis, simple obesity showed a protective trend against cancer in those with respiratory cancers, while abdominal obesity consistently posed a risk for various cancer types., Conclusion: Metabolically unhealthy status and abdominal obesity are risk factors for cancer and all-cause mortality, whereas simple obesity offers protective effects against cancer and all-cause mortality in metabolically unhealthy individuals. These findings suggest that maintaining metabolic health and reducing the metabolic risks associated with abdominal obesity should be key targets for cancer prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Wang, Chen, Liu, Liu, Lin, Xie, Ma, Wang, Shi, Zhang, Yang, Liu, Deng, Zhang and Shi.)

Aims: Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors., Main Methods: In this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors., Key Findings: We observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer., Significance: This study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier Inc.)

Along with discovering cancer biomarkers, non-invasive detection methods have played a critical role in early cancer diagnosis and prognostic improvement. Some traditional detection methods have been used for detecting cancer biomarkers, but they are time-consuming and involve materials and human costs. With great flexibility, sensitivity and specificity, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated system provides a wide range of application prospects in this field. Herein, we introduce the background of the CRISPR-Cas (CRISPR-associated) system and comprehensively summarize the diagnosis strategies of cancer mediated by the CRISPR-Cas system, including four kinds of biochemical-based markers: nucleic acid, enzyme, tumor-specific protein and exosome. Furthermore, we discuss the challenges in implementing the CRISPR-Cas system in clinical applications.

To study the spatial interactions among cancer and non-cancer cells 1 , we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined 'tumour microregions' as spatially distinct cancer cell clusters separated by stromal components. They varied in size and density among cancer types, with the largest microregions observed in metastatic samples. We further grouped microregions with shared genetic alterations into 'spatial subclones'. Thirty five tumour sections exhibited subclonal structures. Spatial subclones with distinct copy number variations and mutations displayed differential oncogenic activities. We identified increased metabolic activity at the centre and increased antigen presentation along the leading edges of microregions. We also observed variable T cell infiltrations within microregions and macrophages predominantly residing at tumour boundaries. We reconstructed 3D tumour structures by co-registering 48 serial ST sections from 16 samples, which provided insights into the spatial organization and heterogeneity of tumours. Additionally, using an unsupervised deep-learning algorithm and integrating ST and CODEX data, we identified both immune hot and cold neighbourhoods and enhanced immune exhaustion markers surrounding the 3D subclones. These findings contribute to the understanding of spatial tumour evolution through interactions with the local microenvironment in 2D and 3D space, providing valuable insights into tumour biology., (© 2024. The Author(s).)

Cancer remains a prominent cause to life expectancy, and targeted cancer therapy stands as a pivotal approach in contemporary therapy. Calcium (Ca 2+ ) signalling plays a multifaceted role in cancer progression, such as proliferation, invasion and distant metastasis. Otherwise, it also exerts an important influence on the efficacy of clinical treatment, including cancer therapy resistance. In this review we discuss the role of the L-type calcium channel CaV1.3 (calcium voltage-gated channel subunit alpha1 D) in different types of cancers, highlighting its potential as a therapeutic target for certain cancer types. The development of selective blockers of the CaV1.3 channel has been of great interest and is expected to be a new option for the treatment of cancers such as prostate cancer and endometrial cancer. We present the pharmacological properties of CaV1.3 and the current status of selective blocker development, and analyse the challenges and possible directions for breakthroughs in the development of tailored medicines., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Immune checkpoint blocking (ICB), a tumor treatment based on the mechanism of T-cell activation, has shown high efficacy in clinical trials, but not all patients benefit from it. Immune checkpoint inhibitors (ICIs) do not respond to cold tumors that lack effective T-cell infiltration but respond well to hot tumors with sufficient T-cell infiltration. How to convert an unresponsive cold tumor into a responsive hot tumor is an important topic in cancer immunotherapy. Ferroptosis, a newly discovered immunogenic cell death (ICD) form, has great potential in cancer therapy. In the process of deeply understanding the mechanism of cold tumor formation, it was found that ferroptosis showed a powerful immune-activating effect by improving T-cell infiltration, and the combination of ICB therapy significantly enhanced the anti-tumor efficacy. This paper reviews the complex relationship between T cells and ferroptosis, as well as summarizes the various mechanisms by which ferroptosis enhances T cell infiltration: reactivation of T cells and reversal of immunosuppressive tumor microenvironment (TME), as well as recent advances of ICI in combination with targeted ferroptosis therapies, which provides guidance for better improving the ICB efficacy of cold tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The Asian Working Group for Cachexia (AWGC) proposed the first consensus report on diagnostic criteria for cachexia in Asians in 2023. However, the current consensus lacks cohort evidence to validate its effectiveness and practicality. We aimed to explore the value of the AWGC2023 criteria for predicting the prognosis and medical burden of patients with cancer through a retrospective post hoc cross-sectional analysis of the Investigation on Nutrition Status and its Clinical Outcome of Common Cancers (INSCOC) project in China., Methods: Cox regression analyses were performed to assess the independent association between cachexia and long-term survival. We utilized C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), inflammatory burden index (IBI), albumin (ALB) and Glasgow prognostic score (GPS) as diagnostic markers for cachexia, designating them as CRP-based cachexia, NLR-based cachexia, IBI-based cachexia, ALB-based cachexia and GPS-based cachexia, respectively. Additionally, we diagnosed cachexia using body mass index (BMI) cutoff values of 18.5, 20, 21 and 22 kg/m 2 , respectively, and subsequently compared their prognostic predictive value through Harrell's concordance index (C-index). Logistic regression models were used to assess the association between cachexia and medical burden., Results: A total of 5426 patients with cancer were enrolled in this study. Cox regression analysis confirmed that cachexia based on the AWGC2023 criteria was an independent predictor of long-term survival in patients with cancer. Patients with cachexia had significantly poorer long-term survival than patients without cachexia (66.4% vs. 49.7%, P < 0.001). Inflammatory biomarker-based cachexia was as an independent predictor of prognosis in patients with cancer, with inflammatory burden index (IBI)-based cachexia demonstrating the optimal prognostic discriminatory ability. The C-index indicated that cachexia based on BMI cutoff values of 18.5, 20, and 22 kg/m 2 did not perform as well as a BMI cutoff value of 21 kg/m 2 . Logistic regression models revealed that using the AWGC2023 criteria, patients with cachexia had a 16.6% higher risk of prolonged hospitalization and a 16.0% higher risk of high medical expenses than patients without cachexia., Conclusion: The AWGC2023 criteria represent a valuable tool for predicting survival and medical burden among Chinese patients with cancer. Encouragement for further validation in other Asian populations is warranted for the AWGC2023 criteria., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

TRAF2 and NCK interacting kinase (TNIK), a critical interacting protein kinase, is currently receiving wide attention. TNIK is found in various human body organs and tissues and participates in cell motility, proliferation, and differentiation. On the one hand, its aberrant expression is related to the onset and progression of numerous malignant tumors. On the other hand, TNIK is important in neuronal growth, proliferation, differentiation, and synaptic formation. Thus, the novel therapeutic strategies for targeting TNIK offer a promising direction for cancer, neurological or psychotic disorders. Here, we briefly summarized the biological information of TNIK, reviewed the role and regulatory mechanism in cancer and neuropsychiatric diseases, and introduced the research progress of inhibitors targeting TNIK. Taken together, this review hopes to contribute to the in-depth understanding of the function and regulatory mechanism of TNIK, which is of great significance for revealing the role of TNIK in the occurrence and treatment of diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the effect of exercise with or without dietary advice on muscle mass, muscle strength and physical functioning (including perceived physical functioning and physical performance) in old cancer survivors., Methods: A systematic literature search was undertaken in May 2022 by searching multiple databases. Randomized controlled trials (RCTs) that compared exercise with or without dietary advice to control group among old cancer survivors were screened. Meta-analyses were conducted to evaluate the effects of exercise with or without dietary advice on muscle mass, muscle strength, and physical functioning., Results: Data from 21 trials were included in this study, including 16 exercise trials and 5 exercise + dietary advice studies. Regarding exercise, evidence supported its significant benefits on muscle strength among old cancer survivors, while no effect was seen on physical functioning and muscle mass. Concerning exercise combined with dietary advice, meta-analysis showed overall benefits on physical functioning, while limited study examined muscle mass and strength. As for safety and feasibility of interventions, low recruitment rate, moderate compliance, and few adverse events were reported., Conclusions: Exercise combined with dietary advice is a more effective approach for old cancer survivors in improving physical functioning compared with exercise alone. Future study is needed to explore the effects of exercise combined with dietary advice on combating sarcopenia. As recruitment and compliance among old cancer survivors were challenging, strategies to stimulate their motivation and promote habitual healthy behaviour are warranted., Implications for Cancer Survivors: It is necessary for old cancer survivors to receive exercise and dietary support to improve physical functioning., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The journey of cancer development is a multifaceted and staged process. The array of treatments available for cancer varies significantly, dictated by the disease's type and stage. Cancer-associated fibroblasts (CAFs), prevalent across various cancer types and stages, play a pivotal role in tumor genesis, progression, metastasis, and drug resistance. The strategy of concurrently targeting cancer cells and CAFs holds great promise in cancer therapy. In this review, we focus intently on CAFs, delving into their critical role in cancer's progression. We begin by exploring the origins, classification, and surface markers of CAFs. Following this, we emphasize the key cytokines and signaling pathways involved in the interplay between cancer cells and CAFs and their influence on the tumor immune microenvironment. Additionally, we examine current therapeutic approaches targeting CAFs. This article underscores the multifarious roles of CAFs within the tumor microenvironment and their potential applications in cancer treatment, highlighting their importance as key targets in overcoming drug resistance and enhancing the efficacy of tumor therapies., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Chromothripsis, a type of complex chromosomal rearrangement originally known as chromoanagenesis, has been a subject of extensive investigation due to its potential role in various diseases, particularly cancer. Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period, leading to complex alterations in one or a few chromosomes. This phenomenon is triggered by chromosome mis-segregation during mitosis. Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges. The association between chromothripsis and cancer has attracted significant interest, with potential implications for tumorigenesis and disease prognosis. This review aims to explore the intricate mechanisms and consequences of chromothripsis, with a specific focus on its association with mitotic perturbations. Herein, we discuss a comprehensive analysis of crucial molecular entities and pathways, exploring the intricate roles of the CIP2A-TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints. Moreover, the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis, paving the way for future therapeutic interventions in various diseases., (© The Author(s) (2024). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Cachexia, which affects 50-80% of cancer patients, is a debilitating syndrome that leads to 20% of cancer-related deaths. A key feature of cachexia is adipose tissue atrophy, but how it contributes to the development of cachexia is poorly understood. Here, we demonstrate in mouse models of cancer cachexia that white adipose tissue browning, which can be a characteristic early-onset manifestation, occurs prior to the loss of body weight and skeletal muscle wasting. By analysing the proteins differentially expressed in extracellular vesicles derived from cachexia-inducing tumours, we identified a molecular chaperone, Glucose-regulated protein 75 (GRP75), as a critical mediator of adipocyte browning. Mechanistically, GRP75 binds adenine nucleotide translocase 2 (ANT2) to form a GRP75-ANT2 complex. Strikingly, stabilized ANT2 enhances its interaction with uncoupling protein 1, leading to elevated expression of the latter, which, in turn, promotes adipocyte browning. Treatment with withanone, a GRP75 inhibitor, can reverse this browning and alleviate cachectic phenotypes in vivo. Overall, our findings reveal a novel mechanism by which tumour-derived GRP75 regulates white adipose tissue browning during cachexia development and suggest a potential white adipose tissue-centred targeting approach for early cachexia intervention., (© 2024. The Author(s).)

Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. The authors conducted a comprehensive review of 75 articles published in PubMed over the past five years. This review was further evaluated in the present paper. Ultimately, it was determined that depression is a prevalent and detrimental phenomenon among cancer patients, particularly those with advanced disease. Consequently, there is a pressing need to prioritize research and interventions aimed at improving the quality of life and psychosocial well-being of cancer patients, including those with advanced disease. The relationship between cancer and depression has been evolving dynamically in recent times. The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Cancer is a leading cause of death worldwide, and the identification of biomarkers and subtypes that can predict the long-term survival of cancer patients is essential for their risk stratification, treatment, and prognosis. However, there are currently no standardized tools for exploring cancer biomarkers or subtypes. In this study, we introduced Cancer Biomarker and subtype Profiler (CBioProfiler), a web server and standalone application that includes two pipelines for analyzing cancer biomarkers and subtypes. The cancer biomarker pipeline consists of five modules for identifying and annotating cancer survival-related biomarkers using multiple survival-related machine learning algorithms. The cancer subtype pipeline includes three modules for data preprocessing, subtype identification using multiple unsupervised machine learning methods, and subtype evaluation and validation. CBioProfiler also includes CuratedCancerPrognosisData, a novel R package that integrates reviewed and curated gene expression and clinical data from 268 studies. These studies cover 43 common blood and solid tumors and draw upon 47,686 clinical samples. The web server is available at https://www.cbioprofiler.com/ and https://cbioprofiler.znhospital.cn/CBioProfiler/, and the standalone app and source code can be found at https://github.com/liuxiaoping2020/CBioProfiler., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007-2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan-Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07-1.14, P < 0.001) and cardiovascular mortality (HR 1.14, 95% CI 1.08-1.21, P < 0.001) in adjusted models. Subgroup analyses revealed that age, sex, smoking status, and hypertension significantly influence NLR's association with cardiovascular mortality. Specific cancers including breast, prostate, non-melanoma skin, colon and melanoma experience increased all-cause and cardiovascular mortality in the higher NLR group compared to lower NLR group. Elevated NLR is a significant predictor of increased mortality in cancer patients, particularly for cardiovascular outcomes. These findings support that NLR acts as a pivotal prognostic tool with significant implications for clinical practice in the realm of cardio-oncology., (© 2024. The Author(s).)

Background: Detection of precachexia is important for the prevention and treatment of cachexia. However, how to identify precachexia is still a challenge., Objective: This study aimed to detect cancer precachexia using a simple method and distinguish the different characteristics of precachexia and cachexia., Methods: We included 3896 participants in this study. We used all baseline characteristics as input variables and trained machine learning (ML) models to calculate the importance of the variables. After filtering the variables based on their importance, the models were retrained. The best model was selected based on the receiver operating characteristic value. Subsequently, we used the same method and process to identify patients with precachexia in a noncachexia population using the same method and process., Results: Participants in this study included 2228 men (57.2%) and 1668 women (42.8%), of whom 471 were diagnosed with precachexia, 1178 with cachexia, and the remainder with noncachexia. The most important characteristics of cachexia were eating changes, arm circumference, high-density lipoprotein (HDL) level, and C-reactive protein albumin ratio (CAR). The most important features distinguishing precachexia were eating changes, serum creatinine, HDL, handgrip strength, and CAR. The two logistic regression models for screening for cachexia and diagnosing precachexia had the highest area under the curve values of 0.830 and 0.701, respectively. Calibration and decision curves showed that the models had good accuracy., Conclusion: We developed two models for identifying precachexia and cachexia, which will help clinicians detect and diagnose precachexia., (© 2024. The Author(s).)

Metabolic reprogramming provides tumors with an energy source and biofuel to support their survival in the malignant microenvironment. Extensive research into the intrinsic oncogenic mechanisms of the tumor microenvironment (TME) has established that cancer-associated fibroblast (CAFs) and metabolic reprogramming regulates tumor progression through numerous biological activities, including tumor immunosuppression, chronic inflammation, and ecological niche remodeling. Specifically, immunosuppressive TME formation is promoted and mediators released via CAFs and multiple immune cells that collectively support chronic inflammation, thereby inducing pre-metastatic ecological niche formation, and ultimately driving a vicious cycle of tumor proliferation and metastasis. This review comprehensively explores the process of CAFs and metabolic regulation of the dynamic evolution of tumor-adapted TME, with particular focus on the mechanisms by which CAFs promote the formation of an immunosuppressive microenvironment and support metastasis. Existing findings confirm that multiple components of the TME act cooperatively to accelerate the progression of tumor events. The potential applications and challenges of targeted therapies based on CAFs in the clinical setting are further discussed in the context of advancing research related to CAFs., (© 2024. The Author(s).)

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Biomolecular condensates or membraneless organelles (MLOs) formed by liquid-liquid phase separation (LLPS) divide intracellular spaces into discrete compartments for specific functions. Dysregulation of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration, tumorigenesis, and many other pathological processes. Herein, we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase separation. We then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders, hearing loss, cancers, and immunological diseases. Finally, we describe the emerging discovery of chemical modulators of phase separation., (© 2024. Science China Press.)

Nanomaterials are extensively used in the diagnosis and treatment of cancer and other diseases because of their distinctive physicochemical properties, including the small size and ease of modification. The approval of numerous nanomaterials for clinical treatment has led to a significant increase in human exposure to these materials. When nanomaterials enter organisms, they interact with DNA, cells, tissues, and organs, potentially causing various adverse effects, such as genotoxicity, reproductive toxicity, immunotoxicity, and damage to tissues and organs. Therefore, it is crucial to elucidate the side effects and toxicity mechanisms of nanomaterials thoroughly before their clinical applications. Although methods for in vitro safety evaluation of nanomaterials are well established, systematic methods for in vivo safety evaluation are still lacking. This review focuses on the in vivo safety evaluation of nanomaterials and explores their potential effects. In addition, the experimental methods for assessing such effects in various disciplines, including toxicology, pharmacology, physiopathology, immunology, and bioinformatics are also discussed., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Purpose: The objective of this study was to determine the recommended Phase 2 dose (RP2D) of pevonedistat, a first in class inhibitor of NEDD8 activating enzyme, in combination with irinotecan (IRN) and temozolomide (TMZ) in children with cancer., Methods: This Phase 1 study used a rolling 6 design to evaluate escalating doses of pevonedistat in combination with standard doses of IRN and TMZ in pediatric patients with recurrent/refractory solid or CNS tumors. During cycle 1, pevonedistat was administered intravenously on days 1, 8, 10, and 12, with IRN (IV, 50 mg/m 2 ) and TMZ (orally, 100 mg/m 2 ), on days 8-12 of a 28-day cycle. In subsequent cycles, pevonedistat was administered on days 1, 3, and 5, with IRN/TMZ on days 1-5 of a 21-day cycle., Results: Thirty patients enrolled; all were eligible and evaluable for toxicity. Six patients each enrolled on pevonedistat dose levels (DL) 1 (15 mg/m 2 ), 2 (20 mg/m 2 ), 3 (25 mg/m 2 ) and 4 (35 mg/m 2 ) as well as an expanded pharmacokinetic (PK) cohort at DL4. The maximum tolerated dose (MTD) was not exceeded. 2/12 (17 %) patients treated at the RP2D (35 mg/m 2 ) experienced a cycle 1 dose limiting toxicity (DLT). IRN is unlikely to affect the pharmacokinetics of pevonedistat. Two patients had a partial response and 6 patients had prolonged stable disease (> 6 cycles)., Conclusions: Pevonedistat in combination with IRN/TMZ is well tolerated in children with solid or CNS tumors. The RP2D of pevonedistat is 35 mg/m 2 on days 1, 3, 5 in combination with IRN/TMZ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The complexity of cancer is intricately linked to its multifaceted biological processes, including the roles of the tumor microenvironment (TME) as well as genetic and metabolic regulation. Histone lactylation has recently emerged as a novel epigenetic modification mechanism that plays a pivotal role in regulating cancer initiation, proliferation, invasion, and metastasis., Objective: This review aims to elucidate the role of histone lactylation in modulating various aspects of tumor biology, including DNA repair mechanisms, glycolytic metabolic abnormalities, functions of non-tumor cells in the TME, and the promotion of tumor inflammatory responses and immune escape. Additionally, the review explores potential therapeutic strategies targeting histone lactylation., Methods: A comprehensive literature review was performed, analyzing recent findings on histone lactylation and its impact on cancer biology. This involved a systematic examination of studies focusing on biochemical pathways, cellular interactions, and clinical implications related to histone lactylation., Results: Histone lactylation was identified as a critical regulator of tumor cell DNA repair mechanisms and glycolytic metabolic abnormalities. It also significantly influences the functions of non-tumor cells within the TME, promoting tumor inflammatory responses and immune escape. Moreover, histone lactylation acts as a multifunctional biological signaling molecule impacting immune responses within the TME. Various cell types within the TME, including T cells and macrophages, were found to regulate tumor growth and immune escape mechanisms through lactylation., Conclusion: Histone lactylation offers a novel perspective on tumor metabolism and its role in cancer development. It presents promising opportunities for the development of innovative cancer therapies. This review underscores the potential of histone lactylation as a therapeutic target, paving the way for new strategies in cancer treatment., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Indeed, tumors are a significant health concern worldwide, and understanding the underlying mechanisms of tumor development is crucial for effective prevention and treatment. Epigenetics, which refers to changes in gene expression that are not caused by alterations in the DNA sequence itself, plays a critical role in the entire process of tumor development. It goes without saying that the effect of methylation on tumors is a significant aspect of epigenetics. Among the methylation modifications, DNA methylation is an important part, which plays a regulatory role in tumor-related genes. Ten-eleven translocation 2 (TET2) is a highly influential protein involved in the modification of DNA methylation. Its primary role is associated with the suppression of tumor development, making it a significant player in cancer research. However, TET2 is frequently mentioned in hematological diseases, its role in solid tumors has received little attention. Studying the changes of TET2 in solid tumors and the regulatory mechanism will facilitate its investigation as a clinical target for targeted therapy and may also provide directions for clinical treatment of malignant tumors., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Chimeric antigen receptor (CAR)-engineered T cells have been defined as 'living drug'. Adding a co-stimulatory domain (CSD) has enhanced the anti-hematological effects of CAR-T cells, thereby elevating their viability for medicinal applications. Various CSDs have helped prepare CAR-T cells to study anti-tumor efficacy. Previous studies have described and summarized the anti-tumor efficacy of CAR-T cells obtained from different CSDs. However, the underlying molecular mechanisms by which different CSDs affect CAR-T function have been rarely reported. The role of CSDs in T cells has been significantly studied, but whether they can play a unique role as a part of the CAR structure remains undetermined. Here, we summarized the effects of CSDs on CAR-T signaling pathways based on the limited references and speculated the possible mechanism depending on the specific characteristics of CAR-T cells. This review will help understand the molecular mechanism of CSDs in CAR-T cells that exert different anti-tumor effects while providing potential guidance for further interventions to enhance anti-tumor efficacy in immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cancer remains a major global health challenge. Immunotherapy has revolutionized the management of cancer, yet only a limited number of patients respond to such treatments. This is largely attributed to the immunosuppressive tumor microenvironment, which diminishes the effectiveness of immunotherapy. Recent studies have underscored the potential of naturally derived caerin 1 peptides, particularly caerin 1.1 and caerin 1.9, which exhibit strong antitumor effects and enhance the efficacy of immunotherapies in animal models. This review encapsulates the current research aimed at augmenting the effectiveness of immunotherapy, focusing on the role of caerin 1.1 and caerin 1.9 in boosting immunotherapeutic outcomes, elucidating possible mechanisms, and discussing their limitations and challenges.

The emergence of spatial multi-omics has helped address the limitations of single-cell sequencing, which often leads to the loss of spatial context among cell populations. Integrated analysis of the genome, transcriptome, proteome, metabolome, and epigenome has enhanced our understanding of cell biology and the molecular basis of human diseases. Moreover, this approach offers profound insights into the interactions between intracellular and intercellular molecular mechanisms involved in the development, physiology, and pathogenesis of human diseases. In this comprehensive review, we examine current advancements in multi-omics technologies, focusing on their evolution and refinement over the past decade, including improvements in throughput and resolution, modality integration, and accuracy. We also discuss the pivotal contributions of spatial multi-omics in revealing spatial heterogeneity, constructing detailed spatial atlases, deciphering spatial crosstalk in tumor immunology, and advancing translational research and cancer therapy through precise spatial mapping., (© 2024. The Author(s).)

Background: Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy., Methods: Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification., Results: Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy., Conclusions: This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes., (© 2024. The Author(s).)

A disintegrin and metalloproteinase domain 10 (ADAM10), a member of the ADAM family, is a cellular surface protein with potential adhesion and protease/convertase functions. The expression regulations in cancers by natural products [adenosine (AD) and its analogs, cordycepin (CD), and N6, N6-dimethyladenosine (m 6 2 A)], and immune regulation are unclear. As results, AD, CD, and m 6 2 A inhibited ADAM10 expression in various cancer cell lines, indicating their roles in anti-cancer agents. Further molecular docking with ADAM10 protein found the binding energies of all docking groups were <-7 kcal/mol for all small-molecules (AD, CD and m 6 2 A), suggesting very good binding activities. In addition, analysis of the immunomodulatory roles in cancer showed that ADAM10 was negatively correlated with immunomodulatory genes such as CCL27, CCL14, CCL25, CXCR5, HLA-B, HLA-DOB1, LAG3, TNFRSF18, and TNFRSF4 in bladder urothelial carcinoma, thymoma, breast invasive carcinoma, TGCT, kidney renal papillary cell carcinoma, SKCM and thyroid carcinoma, indicating the immune-promoting roles for ADAM10. LAG3 mRNA levels were reduced by both AD and CD in vivo . ADAM10 is also negatively associated with tumor immunosuppression and interrelated with the immune infiltration of tumors. Overall, the present study determined ADAM10 expression by AD, CD and m 6 2 A, and in AD or CD/ADAM10/LAG3 signaling in cancers, and suggested a potential method for immunotherapy of cancers by targeting ADAM10 using the small molecules AD, CD and m 6 2 A., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Fu, Du, Liu, Cheng, Wei, Xu and Fu.)

Background: Cancer immunotherapy has made significant progress in recent years, with numerous studies worldwide. Immunotherapy has had a transformative impact on oncology and autoimmune diseases. In the biomedical arena, hydrogels with good properties are widely used in cancer immunotherapy. Our study used bibliometrics to analyze the changing trends in using hydrogels for cancer immunotherapy., Methods: From 2013 to 2023, a systematic search was conducted in the Web of Science Core Collection database to identify reviews and articles discussing the applications of hydrogels in cancer immunotherapy. The software CiteSpace was used to visually perform the bibliometric analysis in terms of research trends, countries, institutions, authors, journals, and keywords. Individual authors' productivity was assessed with the Lotka's law. The most relevant publication sources were identified by Bradford's law., Results: A total of 422 English-language publications related to hydrogels in cancer immunotherapy were collected. The number of annual publications increased rapidly after 2021 and remained constant for the past two years. China published the most articles in this field. The institution with the maximum number of published articles was the Chinese Academy of Sciences in China. Chen. Q was the most prolific author, and Liu. Z was the second most published author. In terms of journal contributions, the journal "Biomaterials" had the highest number of publications (n = 30). Biomaterials, Advanced Functional Materials and Journal of Controlled Release were the most influential journals. Keyword analysis revealed that cancer immunotherapy, drug delivery, immunogenic cell death, tumor microenvironment, injectable hydrogels, and immune checkpoint blockade were the primary research hotspots. In recent 3 years, adoptive T-cell therapy, black phosphorus, cell capture, adaptive cell therapy, tumor microenvironment, photodynamic therapy, and sustained release were the research hotspots in this field. Our study summarizes the objective of hydrogels in cancer immunotherapy in recent years, providing a reference for potential researchers in related field., Conclusion: This bibliometric analysis shows the progress and trend of research on hydrogels in cancer immunotherapy. This study provides a significant avenue for future investigation into current concerns and trends in research within this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhou, Yang and Chen.)

Tumors have always been a major public health concern worldwide, and attempts to look for effective treatments have never ceased. Sialic acid is known to be a crucial element for tumor development and its receptors are highly expressed on tumor-associated immune cells, which perform significant roles in establishing the immunosuppressive tumor microenvironment and further boosting tumorigenesis, progression, and metastasis. Obviously, it is essential to consider sophisticated crosstalk between tumors, the immune system, and preparations, and understand the links between pharmaceutics and immunology. Sialic acid-based chemoimmunotherapy enables active targeting drug delivery via mediating the recognition between the sialic acid-modified nano-drug delivery system represented by liposomes and sialic acid-binding receptors on tumor-associated immune cells, which inhibit their activity and utilize their homing ability to deliver drugs. Such a "Trojan horse" strategy has remarkably improved the shortcomings of traditional passive targeting treatments, unexpectedly promoted tumor shedding, and persistently induced robust immunological memory, thus highlighting its prospective application potential for targeting various tumors. Herein, we review recent advances in sialic acid-based active targeting chemoimmunotherapy to promote tumor shedding, summarize the current viewpoints on the tumor shedding mechanism, especially the formation of durable immunological memory, and analyze the challenges and opportunities of this attractive approach.

Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m 6 A) modification in regulating these processes. This review explores the mechanisms by which m 6 A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m 6 A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m 6 A in vascular-immune crosstalk. Finally, we discuss the current development of m 6 A inhibitors and their potential applications, along with the contribution of m 6 A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m 6 A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m 6 A modulation in cancer treatment. By understanding the intricate role of m 6 A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m 6 A offers a novel approach to interfere with the tumor's ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression., (© 2024. The Author(s).)

Antibody-drug conjugates (ADCs) are biologically targeted drugs composed of antibodies and cytotoxic drugs connected by linkers. These innovative compounds enable precise drug delivery to tumor cells, minimizing harm to normal tissues and offering excellent prospects for cancer treatment. However, monoclonal antibody-based ADCs still present challenges, especially in terms of balancing efficacy and safety. Bispecific antibodies are alternatives to monoclonal antibodies and exhibit superior internalization and selectivity, producing ADCs with increased safety and therapeutic efficacy. In this review, we present available evidence and future prospects regarding the use of bispecific ADCs for cancer treatment, including a comprehensive overview of bispecific ADCs that are currently in clinical trials. We offer insights into the future development of bispecific ADCs to provide novel strategies for cancer treatment., (© 2024. Higher Education Press.)

Background: Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months., Methods: A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB)., Results: A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH., Conclusions: Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

Ferroptosis, a regulated form of cell death, is intricately linked to iron‑dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis as a promising strategy for treating cancers resistant to conventional therapies. A key player in ferroptosis regulation is ferroptosis suppressor protein 1 (FSP1), which promotes cancer cell resistance by promoting the production of the antioxidant form of coenzyme Q10. Of note, FSP1 confers resistance to ferroptosis independently of the glutathione (GSH) and glutathione peroxidase‑4 pathway. Therefore, targeting FSP1 to weaken its inhibition of ferroptosis may be a viable strategy for treating refractory cancer. This review aims to clarify the molecular mechanisms underlying ferroptosis, the specific pathway by which FSP1 suppresses ferroptosis and the effect of FSP1 inhibitors on cancer cells.

Objectives: To assess the feasibility of estimating an EQ-5D-5L value set using a small study design in cancer patients and to compare the EQ-5D-5L values based on the preferences of cancer patients with those of the general public., Methods: Patients with clinically diagnosed cancers were recruited from two hospitals in Shanghai, China. In face-to-face interviews using the EQ-PVT survey, health states were valued by cancer patients using both cTTO and DCE methods. cTTO data was modelled alone or jointly with DCE data. Forty-eight models using different model specifications (cross-attribute level effect [CALE] and additive models), random/fixed effects model assumptions, data heteroscedasticity and censoring were estimated. The best performed model was identified in terms of monotonicity of estimated model coefficients and out-of-sample prediction accuracy., Results: Data collected from 221 cancer patients who participated in the study were included. The hybrid CALE model using both TTO and DCE data performed best in terms of prediction accuracy (Lin's concordance coefficient = 0.989; root mean squared error = 0.058) and suggested that pain/discomfort and anxiety/depression were the most undesirable health problems. Compared to values based on general Chinese public's health preferences, the values based on cancer patients' preferences were much higher and lower for health states characterized by extreme mobility problems and severe/extreme pain or discomfort, respectively., Conclusion: This study demonstrated the feasibility of using a small design to develop EQ-5D-5L value sets based on cancer patients' health preferences. Since there were signs of differences between preferences of patients and general population, it may be valuable to develop patient-specific value sets and use them in clinical decision making and economic evaluations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming of amino acids in tumor cells is intricately linked to protein synthesis, nucleotide synthesis, modulation of signaling pathways, regulation of tumor cell metabolism, maintenance of oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation of amino acid metabolism also impacts tumor microenvironment and tumor immunity. Amino acids can act as signaling molecules that modulate immune cell function and immune tolerance within the tumor microenvironment, reshaping the anti-tumor immune response and promoting immune evasion by cancer cells. Moreover, amino acid metabolism can influence the behavior of stromal cells, such as cancer-associated fibroblasts, regulate ECM remodeling and promote angiogenesis, thereby facilitating tumor growth and metastasis. Understanding the intricate interplay between amino acid metabolism and the tumor microenvironment is of crucial significance. Expanding our knowledge of the multifaceted roles of amino acid metabolism in tumor microenvironment holds significant promise for the development of more effective cancer therapies aimed at disrupting the metabolic dependencies of cancer cells and modulating the tumor microenvironment to enhance anti-tumor immune responses and inhibit tumor progression., (© 2024. The Author(s).)

Background: To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs)., Method: Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials., Result: As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin's and lymphoma, Hodgkin's), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated., Conclusion: ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research., (© 2024. The Author(s).)

Antibody-drug conjugates (ADCs) comprise antibodies, cytotoxic payloads, and linkers, which can integrate the advantages of antibodies and small molecule drugs to achieve targeted cancer treatment. However, ADCs also have some shortcomings, such as non-negligible drug resistance, a low therapeutic index, and payload-related toxicity. Many studies have focused on changing the composition of ADCs, and some have even further extended the concept and types of targeted conjugated drugs by replacing the targeted antibodies in ADCs with peptides, revolutionarily introducing peptide-drug conjugates (PDCs). This Perspective summarizes the current research status of ADCs and PDCs and highlights the structural innovations of ADC components. In particular, PDCs are regarded as the next generation of potential targeted drugs after ADCs, and the current challenges of PDCs are analyzed. Our aim is to offer fresh insights for the efficient design and expedited development of innovative targeted conjugated drugs.

The current research focuses on the effects of nutritional supplementation and exercise on dialysis patients, but whether physical activity (PA) can reduce the risk of adverse outcomes for patients with different nutritional status is not clear. The maintenance hemodialysis (MHD) patients were recruited from April 2021 to April 2022. The information of PA was obtained from the international physical activity questionnaire (IPAQ). The outcomes were cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death. We used COX proportional risk model to estimate the association between PA and the outcomes of MHD patients. Patients are classified into two groups based on geriatric nutritional risk index (GNRI) and classified by age, and we used COX proportional risk model to estimate the association of PA and outcomes in subgroups. The isotemporal substitution model (ISM) was used to estimate the effects of replacing light physical activity (LPA) with moderate physical activity (MPA) or vigorous physical activity (VPA) on risk of cardiovascular events, tumors, and all-cause death in different subgroups. The effects of PA on ankle-brachial index (ABI) and body fat content were analyzed in different IPAQ groups. A total of 241 maintenance hemodialysis patients were included, 105 peoples developed cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death (43.6%). The median follow-up time was 12 months. MPA reduced the risk of outcome in MHD patients or high GNRI patients (40% vs 39%).In MHD patients who was under 65 years with high GNRI, MPA reduced cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death by 55%.PA reduced the risk of cardiovascular event by 65%, but did not reduce the risk of tumor or all-cause death. Replacing LPA with VPA did not improve clinical outcomes. It actually increases the risk of heart failure 0.4%. MPA reduced the risk of cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor, all-cause death in MHD patients under 65 years, while VPA had no health benefit.Trial registration: ChiCTR210050998., (© 2024. The Author(s).)

Objective: To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States. Methods: A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF). Results: In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection. Conclusions: China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.

The Russell mechanism, proposed by Russell, is a cyclic mechanism for the formation of linear tetroxide intermediates, which can spontaneously produce cytotoxic singlet oxygen ( 1 O 2 ) independent of oxygen, suggesting its anticancer potential. Compared with other mainstream anticancer strategies, the Russell mechanism employed for killing cancer cells does not require external energy input, harsh pH condition, and sufficient oxygen. However, up till now, the applications of Russell mechanism in antitumor therapy have been relatively rare, and there is almost no summary of the Russell mechanism in the cancer therapy field. This minireview introduces the different metal elements-based Russell mechanisms and the relevant research progress in Russell mechanism-based cancer therapy in recent years. At the same time, we briefly discussed the current challenges and future development regarding the applications of Russell mechanism. It is hoped that this review can further expand the research of Russell Mechanism in the biomedical field, and inspire researchers to extend its application fields to antibacterial, antiinflammatory, and wound healing uses., (© 2024 Wiley-VCH GmbH.)

Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malignant cells and immune cells at the CS level. We defined a CS-associated signature, called "senescence signature", and found that patients with higher senescence signature had worse prognosis. Higher senescence signature was related to older age, higher genomic instability, longer telomeres, increased lymphocytic infiltration, higher pro-tumor immune infiltrates (Treg cells and MDSCs), and could predict responses to immune checkpoint inhibitor therapy. Single-cell analysis further reveals malignant cells and immune cells share a consistent evolutionary trend at the CS level. MAPK signaling pathway and apoptotic processes may play a key role in CS, and senescence signature may effectively predict sensitivity of MEK1/2 inhibitors, ERK1/2 inhibitors and BCL-2 family inhibitors. We also developed a new CS prediction model of cancer survival and established a portal website to apply this model ( https://bio-pub.shinyapps.io/cs&#95;nomo/ )., (© 2024. The Author(s).)

In contemporary times, tumors have emerged as the primary cause of mortality in the global population. Ongoing research has shed light on the significance of neurotransmitters in the regulation of tumors. It has been established that neurotransmitters play a pivotal role in tumor cell angiogenesis by triggering the transformation of stromal cells into tumor cells, modulating receptors on tumor stem cells, and even inducing immunosuppression. These actions ultimately foster the proliferation and metastasis of tumor cells. Several major neurotransmitters have been found to exert modulatory effects on tumor cells, including the ability to restrict emergency hematopoiesis and bind to receptors on the postsynaptic membrane, thereby inhibiting malignant progression. The abnormal secretion of neurotransmitters is closely associated with tumor progression, suggesting that focusing on neurotransmitters may yield unexpected breakthroughs in tumor therapy. This article presents an analysis and outlook on the potential of targeting neurotransmitters in tumor therapy., Competing Interests: Declaration of Competing Interest We declare that we have no conflicts of interest that could be perceived as influencing the results or recommendations presented in this review. I certify that all information provided in this declaration is true and accurate to the best of my knowledge., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)