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Background: Cardiovascular disease (CVD) and cancer frequently co-occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management., Methods and Results: Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow-up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist-to-hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity-cancer association was estimated using Fine-Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person-years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity-related cancers. Specifically, women with CVD and obesity had increased obesity-related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17-2.31]). No significant associations were found in men, even after excluding prostate cancer., Conclusions: This study suggests that obesity is linked to higher obesity-related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

Background: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex., Methods: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models., Results: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (P interaction  < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape., Conclusions: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account., (© 2024. The Author(s).)

The role of social determinants of health (SDOH) in controlling hypertension (HTN) in cancer patients is unknown. We hypothesize that high SDOH scores correlate with uncontrolled HTN in hypertensive cancer patients. In our prospective study, patients completed the Protocol for Responding to & Assessing Patients' Assets, Risks & Experiences questionnaire. After integrating home and clinic blood pressure readings, uncontrolled HTN was defined as systolic blood pressure greater than or equal to 140 mm Hg and/or diastolic blood pressure greater than or equal to 90 mm Hg. Using Cox regression, we analyzed the impact of SDOH on HTN control, adjusting for relevant factors. The study involved 318 participants (median age 66.4, median follow-up 166 days, SDOH score 6.5 ± 3.2), with stress, educational insecurity, and social isolation as prevalent adverse SDOH. High SDOH scores led to 77% increased risk of uncontrolled HTN (adjusted hazards ratio = 1.77; 95% confidence interval = 1.10 to 2.83, P = .018). Urban residents with high SDOH scores were at an even greater risk. Identifying SDOH and mitigating underlying factors may help control HTN, the most typical disease process treated in all cardio-oncology clinics., (© The Author(s) 2024. Published by Oxford University Press.)

Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly the reprogramming of glucose metabolism, also known as the "Warburg effect". The reprogramming of glucose metabolism is considered a novel hallmark of human cancers. A growing number of studies have shown that reprogramming of glucose metabolism can regulate many biological processes of cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize the major biological functions, clinical significance, potential targets and signaling pathways of glucose metabolic reprogramming in human cancers. Moreover, the applications of natural products and small molecule inhibitors targeting glucose metabolic reprogramming are analyzed, some clinical agents targeting glucose metabolic reprogramming and trial statuses are summarized, as well as the pros and cons of targeting glucose metabolic reprogramming for cancer therapy are analyzed. Overall, the reprogramming of glucose metabolism plays an important role in the prediction, prevention, diagnosis and treatment of human cancers. Glucose metabolic reprogramming-related targets have great potential to serve as biomarkers for improving individual outcomes and prognosis in cancer patients. The clinical innovations related to targeting the reprogramming of glucose metabolism will be a hotspot for cancer therapy research in the future. We suggest that more high-quality clinical trials with more abundant drug formulations and toxicology experiments would be beneficial for the development and clinical application of drugs targeting reprogramming of glucose metabolism.This review will provide the researchers with the broader perspective and comprehensive understanding about the important significance of glucose metabolic reprogramming in human cancers., Competing Interests: Declaration of Competing Interest There are no missing disclosures or conflicts of interest associated with this work. 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.)

Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates., 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 Ltd.. All rights reserved.)

Cancer has a significant negative social and economic impact on both developed and developing countries. As a result, understanding the onset and progression of cancer is critical for developing therapies that can improve the well-being and health of individuals with cancer. With time, study has revealed, the tumor microenvironment has great influence on this process. Micro and nanoscale engineering techniques can be used to study the tumor microenvironment. Nanoscale and Microscale engineering use Novel technologies and designs with small dimensions to recreate the TME. Knowing how cancer cells interact with one another can help researchers develop therapeutic approaches that anticipate and counteract cancer cells' techniques for evading detection and fighting anti-cancer treatments, such as microfabrication techniques, microfluidic devices, nanosensors, and nanodevices used to study or recreate the tumor microenvironment. Nevertheless, a complicated action just like the growth and in cancer advancement, and their intensive association along the environment around it that has to be studied in more detail., Competing Interests: Declaration of Competing Interest The authors state that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Jiang et al.)

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. This review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Background: Previous studies only focused on the individual social factors, without considering the overall social health patterns. The present study aimed to develop an integrated social health score (SHS) and investigate its associations with all-cause, cardiovascular disease (CVD), cancer mortality., Methods: A total of 330,716 participants (mean age 56.3 years; 52.4 % female) from UK Biobank was included between 2006 and 2010, and thereafter followed up to 2021. SHS was calculated by using information on social connections, social engagement and social support. Cox proportional hazards models was used to estimate the hazard ratios and 95 % confidence intervals (CIs) of the association between SHS and all-cause and cause-specific mortality and the 4-way decomposition was used to quantify the mediating effect of lifestyle factors., Results: During a median follow-up period of 12.4 years, 37,897 death cases were recorded, including 4347 CVD and 10,380 cancer cases. The SHS was inversely associated with the risks of all-cause, CVD and cancer mortality in a dose-dependent manner (P for trend <0.001). The association between SHS with all-cause mortality was mediated by lifestyle factors including diet score, smoking status and alcohol consumption., Conclusion: Integrated SHS was inversely associated with risks of all-cause, CVD and cancer mortality, and the associations were partially mediated by lifestyle factors. Our study highlights the importance of maintaining high levels of social health by jointly enhancing social involvement, expanding social networks, and cultivating enduring intimate relationships across the life course., 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 B.V. All rights reserved.)

Background: Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Although our previous study detected a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between CVD, cardiovascular risk factors, and cancer mortality., Methods and Results: A prospective cohort study using data from the continuous NHANES (National Health and Nutrition Examination Survey, 1999-2016) merged with Medicare and National Death Index mortality data, through December 31, 2018. We included individuals with no history of cancer at baseline. The primary exposure was CVD at baseline. We also conducted a comprehensive risk factor analysis as secondary exposure. The main outcome was cancer mortality data collected from Medicare and National Death Index. We included 44 591 adult individuals representing 1 738 423 317 individuals (52% female, 67% non-Hispanic White, and 9% Hispanic). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (adjusted hazard ratio [aHR], 1.37 [95% CI 1.07-1.76], P =0.01) after adjusting for age, sex, and race and ethnicity. Notably, cancer mortality increased with aging (aHR, 1.08 [95% CI 1.05-1.11], P <0.0001), current smoking status (aHR, 6.78 [95% CI, 3.43-13.42], P <0.0001), and obesity (aHR, 2.32 [95% CI, 1.13-4.79], P =0.02). Finally, a significant interaction ( P =0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal body mass index (aHR, 1.73 [95% CI, 1.03-2.91], P =0.04)., Conclusions: Our study highlights the close relationship between cardiovascular health and cancer mortality. Our findings suggest that obesity may play a significant role in cancer mortality among individuals with CVD. These findings emphasize the need for a more proactive approach in managing the shared risk factors for CVD and cancer.

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).)

Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, the mechanisms governing metastasis are not fully elucidated. Contemporary findings in the domain of cancer biology have shed light on the molecular aspects of this intricate process. Tumor cells undergoing invasion engage with other cellular entities and proteins en route to their destination. Insights into these engagements have enhanced our comprehension of the principles directing the movement and adaptability of metastatic cells. The tumor microenvironment plays a pivotal role in facilitating the invasion and proliferation of cancer cells by enabling tumor cells to navigate through stromal barriers. Such attributes are influenced by genetic and epigenetic changes occurring in the tumor cells and their surrounding milieu. A profound understanding of the metastatic process's biological mechanisms is indispensable for devising efficacious therapeutic strategies. This review delves into recent developments concerning metastasis-associated genes, important signaling pathways, tumor microenvironment, metabolic processes, peripheral immunity, and mechanical forces and cancer metastasis. In addition, we combine recent advances with a particular emphasis on the prospect of developing effective interventions including the most popular cancer immunotherapies and nanotechnology to combat metastasis. We have also identified the limitations of current research on tumor metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers and early detection methods, as well as heterogeneity among others. It is anticipated that this comprehensive review will significantly contribute to the advancement of cancer metastasis research., (© 2024. The Author(s).)

The tumor microenvironment (TME) is a highly heterogeneous ecosystem that plays critical roles in the initiation, progression, invasion, and metastasis of cancers. Extracellular vesicles (EVs), as emerging components of the host-tumor communication, are lipid-bilayer membrane structures that are secreted by most cell types into TEM and increasingly recognized as critical elements that regulate the interaction between tumor cells and their surroundings. They contain a variety of bioactive molecules, such as proteins, nucleic acids, and lipids, and participate in various pathophysiological processes while regulating intercellular communication. While many studies have focused on the EVs derived from different body fluids or cell culture supernatants, the direct isolation of tissue-derived EVs (Ti-EVs) has garnered more attention due to the advantages of tissue specificity and accurate reflection of tissue microenvironment. In this review, we summarize the protocol for isolating Ti-EVs from different tissue interstitium, discuss the role of tumor-derived and adipose tissue-derived Ti-EVs in regulating TME. In addition, we sum up the latest application of Ti-EVs as potential biomarkers for cancer diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nutrient bioavailability in the tumor microenvironment plays a pivotal role in tumor proliferation and metastasis. Among these nutrients, glutamine is a key substance that promotes tumor growth and proliferation, and its downstream metabolite asparagine is also crucial in tumors. Studies have shown that when glutamine is exhausted, tumor cells can rely on asparagine to sustain their growth. Given the reliance of tumor cell proliferation on asparagine, restricting its bioavailability has emerged as promising strategy in cancer treatment. For instance, the use of asparaginase, an enzyme that depletes asparagine, has been one of the key chemotherapies for acute lymphoblastic leukemia (ALL). However, tumor cells can adapt to asparagine restriction, leading to reduced chemotherapy efficacy, and the mechanisms by which different genetically altered tumors are sensitized or adapted to asparagine restriction vary. We review the sources of asparagine and explore how limiting its bioavailability impacts the progression of specific genetically altered tumors. It is hoped that by targeting the signaling pathways involved in tumor adaptation to asparagine restriction and certain factors within these pathways, the issue of drug resistance can be addressed. Importantly, these strategies offer precise therapeutic approaches for genetically altered cancers., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronavirus pandemic, the development of mRNA vaccines has seen substantial progress and widespread adoption. In the present review, the development of mRNA vaccines, their mechanisms of action, factors influencing their function and the current clinical applications of the vaccine are discussed. A focus is placed on the application of mRNA vaccines in cancer, with the aim of highlighting unique advances and the remaining challenges of this novel and promising therapeutic approach.

Despite the considerable potential of immune checkpoint blockade (ICB) therapy in treating various cancer types, it faces several challenges, of which the constrained objective response rate and relatively short duration of response observed in patients with cancer are the most important. This study introduces an injectable temperature-sensitive hydrogel, Pluronic F-127 (PF-127)@MnCl 2 / alginate microspheres (ALG-MS)@MgCl 2 , that enhances the therapeutic efficacy of programmed cell death-ligand 1 (PD-L1) in cancer cells. The hydrogel material used in this study facilitated the rapid release of a significant amount of manganese ions (Mn 2+ ) and the gradual and sustained release of magnesium ions (Mg 2+ ) within the tumor microenvironment. This staged release profile promotes an immune microenvironment conducive to the cytotoxicity of CD8 + T cells and natural killer cells, thereby enhancing the efficacy of ICB therapy. Furthermore, the PF-127@MnCl 2 /ALG-MS@MgCl 2 composite hydrogel exhibits the ability to convert drug-resistant tumor ("cold tumor") with a low PD-L1 response to a "hot tumor" with a high PD-L1 response. In summary, the PF-127@MnCl 2 /ALG-MS@MgCl 2 hydrogel manipulates the immune microenvironment through the precise discharge of Mg 2+ and Mn 2+ , thus, augmenting the efficacy of ICB therapy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Single-atom enzymes (SAzymes) exhibit great potential for chemodynamic therapy (CDT); while, general application is still challenged by their instability and unavoidable side effects during delivery. Herein, a manganese-based polyoxometalate single-atom enzyme (Mn-POM SAE) is first introduced into tumor-specific CDT, which exhibits tumor microenvironment (TME)-activated transition of nontoxicity-to-toxicity. Different from traditional POM materials, the aggregates of low-toxic Mn-POM SAE nanospheres are obtained at neutral conditions, facilitating efficient delivery and avoiding toxicity problems in normal tissues. Under acid TME conditions, these nanospheres are degraded into smaller units of toxic Mn(II)-PW 11 ; thus, initiating cancer cell-specific therapy. The released active units of Mn(II)-PW 11 exhibit excellent multienzyme-like activities (including peroxidase (POD)-like, oxidase (OXD)-like, catalase (CAT)-like, and glutathione peroxidase (Gpx)-like activities) for the synergistic cancer therapy due to the stabilized high valence Mn species (Mn III /Mn IV ). As demonstrated by both intracellular evaluations and in vivo experiments, ROS is generated to cause damage to lysosome membranes, further facilitating acidification and impaired autophagy to enhance cancer therapy. This study provides a detailed investigation on the acid-triggered releasing of active units and the electron transfer in multienzyme-mimic-like therapy, further enlarging the application of POMs from catalytical engineering into cancer therapy., (© 2024 Wiley‐VCH GmbH.)

Extracellular vesicles (EVs) are important carriers of signaling molecules, such as nucleic acids, proteins, and lipids, and have become a focus of increasing interest due to their numerous physiological and pathological functions. For a long time, most studies on EV components focused on noncoding RNAs; however, in recent years, extracellular vesicle proteins (EVPs) have been found to play important roles in diagnosis, treatment, and drug resistance and thus have been considered favorable biomarkers and therapeutic targets for various tumors. In this review, we describe the general protocols of research on EVPs and summarize their multifaceted roles in precision medicine applications, including cancer diagnosis, dynamic monitoring of therapeutic efficacy, drug resistance research, tumor microenvironment interaction research, and anticancer drug delivery., (© 2024. The Author(s).)

Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles in tumor diagnosis and treatment lie in their ability to target drug delivery, minimizing toxicity to normal tissues while enhancing therapeutic efficacy. Moreover, their responsiveness to both endogenous and exogenous stimuli opens up new possibilities for integrating multiple treatment modalities. This review scrutinizes the burgeoning utility of degradable silica nanoparticles in combination with chemotherapy and other treatment modalities. Commencing the elucidation of degradable silica synthesis and degradation mechanisms, emphasis is placed on the responsiveness of these materials to endogenous (e.g., pH, redox reactions, hypoxia, and enzymes) and exogenous stimuli (e.g., light and high-intensity focused ultrasound). Moreover, this exploration delves into strategies harnessing degradable silica nanoparticles in chemotherapy alone, coupled with radiotherapy, photothermal therapy, photodynamic therapy, gas therapy, immunotherapy, starvation therapy, and chemodynamic therapy, elucidating multimodal synergies. Concluding with an assessment of advances, challenges, and constraints in oncology, despite hurdles, future investigations are anticipated to augment the role of degradable silica in cancer therapy. These insights can serve as a compass for devising more efficacious combined tumor treatment strategies., (© 2024 Wiley‐VCH GmbH.)

Alternative polyadenylation (APA) is a crucial mechanism for regulating gene expression during pre-mRNA 3' processing. Pre-mRNA 3' end processing factors is the main factor involved in this process. However, pre-mRNA 3' end processing factors in different cancer expression profiles and the relationship between pre-mRNA 3' end processing factors and tumor microenvironment and the prognosis of the same patient is still unclear. In this study, we conducted a comprehensive exploration of the core pre-mRNA 3' end processing factors across various cancer types by utilizing common cancer database, and revealing a robust correlation between the expression of these core factors and tumor characteristics. Leveraging advanced bioinformatics databases, we evaluated the expression levels and prognostic relevance of pre-mRNA 3' end processing factors across pan-cancer tissues. Our extensive pan-cancer analysis revealed unique expression patterns of pre-mRNA 3' end processing factors in both tumor and adjacent non-tumorous tissues. Notably, we found a significant correlation between the expression levels of pre-mRNA 3' end processing factors and patient prognosis. Furthermore, we identified strong associations between pre-mRNA 3' end processing factors expression and various factors, such as stromal, immune, RNA stemness, and DNA stemness scores across pan-cancer tissues. Our data also highlighted a link between the expression of pre-mRNA 3' end processing factors and sensitivity to specific drugs, including pyrazoloacndine, amonaflide, and chelerythrinede, among others. We found four key pre-mRNA 3' end processing factors that play a crucial role in mRNA preprocessing. Our study illuminates the potential promotion and inhibition role of pre-mRNA 3' end processing regulators in the progression of cancer, CPSF2, CPSF3, CSTF2, SYMPK offering valuable insights for future research investigations on these regulators as diagnostic markers and therapeutic targets across pan-cancer., (© 2024. The Author(s).)

Background: Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. However, the distribution and molecular characteristics of EGFR fusions in Chinese patients with solid malignancies have not been explored., Methods: Panel-based next-generation sequencing (NGS) data of 35,023 patients with various types of solid tumors was collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS)., Results: In this study, prevalence of functional EGFR fusions was 0.303% (106/35,023) in total across solid tumors, which occur more commonly in gastroesophageal junction cancer (1/61, 1.613%), followed by medulloblastoma (1/66, 1.515%) and glioma (33/2409, 1.370%). Analysis showed a prevalence for fusion partners in different tumor types. The top 3 co-mutant genes with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). Furthermore, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p < 0.0001) in the TCGA cohort, suggesting that EGFR fusion might be a high-risk factor for poor prognosis., Conclusions: Our study is the first retrospective analysis of EGFR fusions in a large-scale solid tumor population, which may provide a reference for future EGFR-TKI clinical trials with EGFR fusions., (© 2024. The Author(s).)

Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, a narrow therapeutic window, and unfavorable pharmacokinetic properties. To solve the above problems, target drug delivery to tumor cells, and reduce the side effects of drugs, an anti-tumor drug delivery system based on tumor microenvironment has become a focus of research in recent years. The construction of a reduction-sensitive nanomedicine delivery system based on disulfide bonds has attracted much attention. Disulfide bonds have good reductive responsiveness and can effectively target the high glutathione (GSH) levels in the tumor environment, enabling precise drug delivery. To further enhance targeting and accelerate drug release, disulfide bonds are often combined with pH-responsive nanocarriers and highly expressed ligands in tumor cells to construct drug delivery systems. Disulfide bonds can connect drug molecules and polymer molecules in the drug delivery system, as well as between different drug molecules and carrier molecules. This article summarized the drug delivery systems (DDS) that researchers have constructed in recent years based on disulfide bond drug delivery systems targeting the tumor microenvironment, disulfide bond cleavage-triggering conditions, various drug loading strategies, and carrier design. In this review, we also discuss the controlled release mechanisms and effects of these DDS and further discuss the clinical applicability of delivery systems based on disulfide bonds and the challenges faced in clinical translation., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ma et al.)

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.

Tumor vessels characterized by abnormal functions and structures hinder the infiltration and immune antigen presentation of immune cells by inducing the formation of an immunosuppressive microenvironment ("cold" environment). Vascular-targeted therapy has been proven to enhance immune stimulation and the effectiveness of immunotherapy by modulating the "cold" microenvironment, such as hypoxia and an acidic microenvironment. Notably, a therapeutic strategy based on "vascular-immune" crosstalk can achieve dual regulation of tumor vessels and the immune system by reprogramming the tumor microenvironment (TME), thus forming a positive feedback loop between tumor vessels and the immune microenvironment. From this perspective, we discuss the factors of tumor angiogenesis and "cold" TME formation. Building on this foundation, some vascular-targeted therapeutic drugs will be elaborated upon in detail to achieve dual regulation of tumor vessels and immunity. More importantly, we focus on cutting-edge nanotechnology in view of "vascular-immune" crosstalk and discuss the rational fabrication of tailor-made nanosystems for efficiently enhancing immunotherapy., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Jiang et al.)

Mechanical properties, as crucial physical properties, have a significant impact on the occurrence, development, and metastasis of tumors. Regulating the mechanical properties of tumors to enhance their sensitivity to radiotherapy and chemotherapy has become an important strategy in the field of cancer treatment. Over the past few decades, nanomaterials have made remarkable progress in cancer therapy, either based on their intrinsic properties or as drug delivery carriers. However, the investigation of nanomaterials of mechanical regulation in tumor therapy is currently in its initial stages. The mechanical properties of nanomaterials themselves, drug carrier targeting, and regulation of the mechanical environment of tumor tissue have far-reaching effects on the efficient uptake of drugs and clinical tumor treatment. Therefore, this review aims to comprehensively summarize the applications and research progress of nanomaterials in tumor therapy based on the regulation of mechanical properties, in order to provide strong support for further research and the development of treatment strategies in this field.

Objective: Unsafe opioid-related practices can lead to abuse, diversion, and accidental overdoses. In this study, we aimed to describe the patterns and beliefs regarding the storage, disposal, and use of opioids among Chinese patients with cancer in their home settings, which remain unclear., Methods: A multicenter cross-sectional survey was conducted in Hubei Province from October 2022 to June 2023. We collected information on the storage, disposal, and use of opioids among cancer pain inpatients in the oncology department. Logistic regression was used to estimate the factors associated with unsafe disposal and use of opioids., Results: The survey included 221 patients with a median age of 62 years. Only 3.2% stored their opioids under lock and key, and 49.8% were unaware of proper disposal methods. Nearly one-fifth (19.5%) reported having received information on the safe storage (14.0%) and/or disposal (10.0%) of opioids. A total of 44.3% reported unsafe use by sharing (1.8%), losing (4.1%), or taking opioids at a higher dose than prescribed (42.5%). Patients who did not receive information on the safe disposal of opioids (OR = 4.57, P = .0423), had a history of alcohol use (OR = 1.91, P = .0399), and used opioids other than morphine (OR = 2.31, P = .0461) had higher odds of unsafe disposal practices. Individuals with an associate degree/bachelor's degree or above were less likely to dispose of (OR = 0.36, P = .0261) and use (OR = 0.31, P = .0127) opioids unsafely., Conclusion: A significant proportion of Chinese patients with cancer exhibit unsafe practices in the storage, disposal, and use of opioids. The study highlights an urgent need for implementing routine education programs and drug "take-back" initiatives to improve opioid-related practices., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Expanding access to clinical trials in community settings is a potential approach to addressing disparities in accrual of historically underrepresented populations. However, little is known about the characteristics of practices that do not participate in research. We investigated differences in patient and practice characteristics of US community oncology practices with high vs low engagement in clinical research., Methods: We included patients from a real-world, nationwide electronic health record-derived, de-identified database who received active treatment for cancer at community oncology practices between November 1, 2017, and October 31, 2022. We assessed patient and practice characteristics and their associations with high vs low research engagement using descriptive analyses and logistic regression models., Results: Of the 178 practices, 70 (39.3%) events had high research engagement, treated 57.8% of the overall 568 540 patient cohort, and enrolled 3.25% of their patients on cancer treatment trials during the 5-year observation period (vs 0.27% enrollment among low engagement practices). Practices with low vs high research engagement treated higher proportions of the following patient groups: ages 75 years and older (24.2% vs 21.8%), non-Latinx Black (12.6% vs 10.3%) or Latinx (11.6% vs 6.1%), were within the lowest socioeconomic status quintile (21.9% vs16.5%), and were uninsured or had no documented insurance (22.2% vs 13.6%)., Conclusions: Patient groups historically underrepresented in oncology clinical trials are more likely to be treated at community practices with limited or no access to trials. These results suggest that investments to expand the clinical research footprint among practices with low research engagement could help address persistent inequities in trial representation., (© The Author(s) 2024. Published by Oxford University Press.)

Metabolic reprogramming has been demonstrated to have a significant impact on the biological behaviors of tumor cells, among which glycolysis is an important form. Recent research has revealed that the heightened glycolysis levels, the abnormal expression of glycolytic enzymes, and the accumulation of glycolytic products could regulate the growth, proliferation, invasion, and metastasis of tumor cells and provide a favorable microenvironment for tumor development and progression. Based on the distinctive glycolytic characteristics of tumor cells, novel imaging tests have been developed to evaluate tumor proliferation and metastasis. In addition, glycolytic enzymes have been found to serve as promising biomarkers in tumor, which could provide assistance in the early diagnosis and prognostic assessment of tumor patients. Numerous glycolytic enzymes have been identified as potential therapeutic targets for tumor treatment, and various small molecule inhibitors targeting glycolytic enzymes have been developed to inhibit tumor development and some of them are already applied in the clinic. In this review, we systematically summarized recent advances of the regulatory roles of glycolysis in tumor progression and highlighted the potential clinical significance of glycolytic enzymes and products as novel biomarkers and therapeutic targets in tumor treatment., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

Purpose: Tiragolumab is an immunoglobulin G1 monoclonal antibody targeting the immune checkpoint T cell immunoreceptor with immunoglobulin and immunoreceptor ITIM domains. Targeting multiple immune pathways may improve anti-tumor responses. The phase I YP42514 study assessed the pharmacokinetics (PK), safety, and preliminary efficacy of tiragolumab plus atezolizumab in Chinese patients with advanced solid tumors., Methods: Adult patients from mainland China with Eastern Cooperative Oncology Group performance score 0/1, life expectancy of ≥ 12 weeks, and adequate hematologic/end organ function were eligible. Patients received tiragolumab 600 mg and atezolizumab 1200 mg intravenous every 3 weeks. Key endpoints were PK (serum concentrations of tiragolumab and atezolizumab) and safety. Results from this study were compared with the global phase I study, GO30103 (NCT02794571)., Results: In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of patients were male and the most common tumor type was non-small cell lung cancer. Exposures in Chinese patients were comparable to the global GO30103 population: geometric mean ratio was 1.07 for Cycle 1 tiragolumab area under the concentration-time curve 0-21 and 0.92 and 0.93 for Cycle 1 peak and trough atezolizumab exposure, respectively. Treatment-related adverse events were consistent across the Chinese and global populations. Two patients (10.0%) in this study achieved a partial response., Conclusion: In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or safety of tiragolumab plus atezolizumab between the Chinese and global populations., Clinical Trial Registration Number: China Clinical Trial Registry Identifier CTR20210219/YP42514. Date of registration 16 March 2021., (© 2024. The Author(s).)

MicroRNAs (miRNAs) are a group of non‑coding RNAs that exert master regulatory functions in post‑-transcriptional gene expression. Accumulating evidence shows that miRNAs can either promote or suppress tumorigenesis by regulating different target genes or pathways and may be involved in the occurrence of carcinoma. miR‑409‑3p is dysregulated in a variety of malignant cancers. It plays a fundamental role in numerous cellular biological processes, such as cell proliferation, apoptosis, migration, invasion, autophagy, angiogenesis and glycolysis. In addition, studies have shown that miR‑409‑3p is expected to become a non‑invasive biomarker. Identifying the molecular mechanisms underlying miR‑409‑3p‑mediated tumor progression will help investigate miR‑409‑3p‑based targeted therapy for human cancers. The present review comprehensively summarized the recently published literature on miR‑409‑3p, with a focus on the regulation and function of miR‑409‑3p in various types of cancer, and discussed the clinical implications of miR‑409‑3p, providing new insight for the diagnosis and treatment of cancers.

Introduction: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database., Methods: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database., Results: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation., Conclusion: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months., Registration: PROSPERO (CRD42022385274).

Importance: Two prominent organizations, the American Society of Clinical Oncology and the National Quality Forum (NQF), have developed a cancer quality metric aimed at reducing systemic anticancer therapy administration at the end of life. This metric, NQF 0210 (patients receiving chemotherapy in the last 14 days of life), has been critiqued for focusing only on care for decedents and not including the broader population of patients who may benefit from treatment., Objective: To evaluate whether the overall population of patients with metastatic cancer receiving care at practices with higher rates of oncologic therapy for very advanced disease experience longer survival., Design, Setting, and Participants: This nationwide population-based cohort study used Flatiron Health, a deidentified electronic health record database of patients diagnosed with metastatic or advanced disease, to identify adult patients (aged ≥18 years) with 1 of 6 common cancers (breast cancer, colorectal cancer, non-small cell lung cancer [NSCLC], pancreatic cancer, renal cell carcinoma, and urothelial cancer) treated at health care practices from 2015 to 2019. Practices were stratified into quintiles based on retrospectively measured rates of NQF 0210, and overall survival was compared by disease type among all patients treated in each practice quintile from time of metastatic diagnosis using multivariable Cox proportional hazard models with a Bonferroni correction for multiple comparisons. Data were analyzed from July 2021 to July 2023., Exposure: Practice-level NQF 0210 quintiles., Main Outcome and Measure: Overall survival., Results: Of 78 446 patients (mean [SD] age, 67.3 [11.1] years; 52.2% female) across 144 practices, the most common cancer types were NSCLC (34 201 patients [43.6%]) and colorectal cancer (15 804 patients [20.1%]). Practice-level NQF 0210 rates varied from 10.9% (quintile 1) to 32.3% (quintile 5) for NSCLC and 6.8% (quintile 1) to 28.4% (quintile 5) for colorectal cancer. No statistically significant differences in survival were observed between patients treated at the highest and the lowest NQF 0210 quintiles. Compared with patients seen at practices in the lowest NQF 0210 quintiles, the hazard ratio for death among patients seen at the highest quintiles varied from 0.74 (95% CI, 0.55-0.99) for those with renal cell carcinoma to 1.41 (95% CI, 0.98-2.02) for those with urothelial cancer. These differences were not statistically significant after applying the Bonferroni-adjusted critical P = .008., Conclusions and Relevance: In this cohort study, patients with metastatic or advanced cancer treated at practices with higher NQF 0210 rates did not have improved survival. Future efforts should focus on helping oncologists identify when additional therapy is futile, developing goals of care communication skills, and aligning payment incentives with improved end-of-life care.

Background: The risk factors for skin injuries remain poorly understood in cancer patients with peripherally inserted central catheters (PICC). We herein aimed at exploring the effect of clinical factors on the risk of PICC-related skin injuries., Methods: We included 1245 cancer patients with PICC from 16 hospitals in Suzhou, China. The study outcome was in-hospital skin injuries, including contact dermatitis, skin (epidermal) stripping, tension injury, allergic dermatitis, skin tear, maceration, folliculitis, and pressure injury., Results: During hospitalization, 274 patients (22.0%) developed skin injuries after prolonged use of an indwelling catheter. Univariable logistic regression analysis identified several risk factors for PICC-related skin injuries; multivariable logistic regression analysis showed that the following factors independently and significantly ( p  < 0.05) associated with the risk of PICC-related skin injuries: body mass index (BMI, >25 kg/m 2 versus <18.5 kg/m 2 : odds ratio (OR), 1.79; 95% confidence interval (CI), 1.03-3.11), skin condition (humid vs normal: OR, 2.96; 95% CI, 1.62-5.43), skin indentation (OR, 4.67; 95% CI, 3.31-6.58), allergic history (OR, 2.11; 95% CI, 1.21-3.66), history of dermatitis (OR, 3.05; 95% CI, 1.00-9.28), history of eczema (OR, 3.36; 95% CI, 1.20-9.43), catheter insertion site (under elbow vs . upper arm: OR, 3.32; 95% CI, 1.12-9.90), and PICC maintenance interval (4-5 days vs ⩽3 days: OR, 0.06; 95% CI, 0.01-0.50; 5-7 days vs ⩽3 days: OR, 0.07; 95% CI, 0.02-0.31; 7-9 days vs ⩽3 days: OR, 0.10; 95% CI, 0.02-0.57)., Conclusions: BMI, skin condition, skin indentation, allergic history, history of dermatitis, history of eczema, catheter insertion site, and PICC maintenance interval were independent risk factors for PICC-related skin injuries in cancer patients. This knowledge will guide future studies with formulating optimal treatment strategies for improving the skin health of cancer patients with PICC., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Despite significant advances in cancer immunotherapy over the past decades, such as T cell-engaging chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockade (ICB), therapeutic failure resulting from various factors remains prevalent. Therefore, developing combinational immunotherapeutic strategies is of great significance for improving the clinical outcome of cancer immunotherapy. Natural products are substances that naturally exist in various living organisms with multiple pharmacological or biological activities, and some of them have been found to have anti-tumor potential. Notably, emerging evidences have suggested that several natural compounds may boost the anti-tumor effects through activating immune response of hosts, in which CD8 + T cells play a pivotal role., Methods: The data of this review come from PubMed, Web of Science, Google Scholar, and ClinicalTrials (https://clinicaltrials.gov/) with the keywords "CD8 + T cell", "anti-tumor", "immunity", "signal 1", "signal 2", "signal 3", "natural products", "T cell receptor (TCR)", "co-stimulation", "co-inhibition", "immune checkpoint", "inflammatory cytokine", "hesperidin", "ginsenoside", "quercetin", "curcumin", "apigenin", "dendrobium officinale polysaccharides (DOPS)", "luteolin", "shikonin", "licochalcone A", "erianin", "resveratrol", "procyanidin", "berberine", "usnic acid", "naringenin", "6-gingerol", "ganoderma lucidum polysaccharide (GL-PS)", "neem leaf glycoprotein (NLGP)", "paclitaxel", "source", "pharmacological activities", and "toxicity". These literatures were published between 1993 and 2023., Results: Natural products have considerable advantages as anti-tumor drugs based on the various species, wide distribution, low price, and few side effects. This review summarized the effects and mechanisms of some natural products that exhibit anti-tumor effects via targeting CD8 + T cells, mainly focused on the three signals that activate CD8 + T cells: TCR, co-stimulation, and inflammatory cytokines., Conclusion: Clarifying the role and underlying mechanism of natural products in cancer immunotherapy may provide more options for combinational treatment strategies and benefit cancer therapy, to shed light on identifying potential natural compounds for improving the clinical outcome in cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this review., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Comprehensive genomic profiling (CGP) provides new opportunities for patients with advanced cancer to receive genome-matched therapies, but the availability rate of these remains low. We reviewed our CGP cases and suggested possible strategies to improve the current status from a clinical perspective., Methods: Druggable genomic alterations and barriers to accessing genome-matched therapies were investigated in 653 patients with 30 various types of cancers who underwent CGP., Results: While the availability rate of genome-matched therapies as a whole was 9.5%, CGP was useful in some cancer types. Patients with thyroid cancer and lung cancer harbored druggable genomic alterations at high rates, while sarcoma rarely harbored these alterations (100%, 76%, and 15.2%, respectively). In contrast, the availability rate of genome-matched therapies was highest in patients with sarcoma and head and neck cancer (HNC) (60% and 40%, respectively). One hundred thirteen patients (63.5%) had multiple barriers to accessing genome-matched therapy. Of 178 patients, 21 patients (11.8%) could not be considered for genome-matched therapies solely because of the deterioration of their performance status., Conclusion: This study demonstrated the usefulness of CGP for patients with sarcoma and HNC in addition to lung cancer in clinical practice. Performing CGP at the front line has the potential to improve the availability of genome-matched therapy., (© 2024. The Author(s).)

Objective: Walking pace is associated with risks of major chronic diseases including cancer, cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) in the general population. However, whether increasing walking pace could reduce risks of major chronic diseases in individuals with hypertension remains to be explored, and the underlying mechanism potentially mediated by low-grade inflammation is also unclear., Methods: A total of 160,470 participants with hypertension were included based on the UK Biobank. The relationships of the walking pace and low-grade inflammation with risks of major chronic diseases in individuals with hypertension were assessed by the Cox proportional hazards model. Mediation analyses were performed to investigate the contribution of low-grade inflammation to the association between walking pace and risks of major chronic diseases., Results: Individuals with hypertension at the brisk walking pace had decreased risks of overall cancer and site-specific cancers (liver, lung, and endometrial cancers), all CVD events (angina, atrial fibrillation, heart failure, myocardial infarction, peripheral vascular disease and stroke), and T2DM (hazard ratios: 0.42-0.91). Increasing low-grade inflammation was associated with higher risks of aforementioned diseases except liver cancer and atrial fibrillation. Furthermore, low-grade inflammation partially mediated associations of the walking pace with risks of lung cancer, T2DM, and all CVD events (except atrial fibrillation), with mediation proportion of 2.0%-9.8%., Conclusions: Brisk walking pace was linked to reduced risks of major chronic diseases in individuals with hypertension, partially mediated by low-grade inflammation. Improving walking pace may be beneficial for health in individuals with hypertension., 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.)

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.)

The surface physiochemical properties of nanomedicine play a crucial role in modulating biointerfacial reactions in sequential biological compartments, accordingly accomplishing the desired programmed delivery scenario to intracellular targets. PEGylation, which involves modifying the surface with a layer of poly(ethylene glycol), has been validated as an effective strategy for minimizing adverse biointerfacial interactions. However, it has also been observed to impede cellular uptake and intracellular trafficking activities. To address this dilemma, we propose a dynamic surface chemistry approach that actively prevents non-specific reactions in systemic circulation, while readily facilitating cellular uptake by converting into a highly cytomembrane-adhesive state. Moreover, the surface becomes more adhesive to endolysosomal membranes, enabling translocation into the cytosol. In this study, PEGylated mRNA delivery nanoparticulates were tethered with charge-reversible polymers to create dynamic surroundings through click chemistry. Importantly, the dynamic surroundings exhibited negative charges under physiological conditions (pH 7.4). This property prevented degradation by anionic nucleases and structural disassembly induced by endogenous charged biological species. Consequently, the nanoparticles exhibited appreciable stealth function, effectively managing the first pass effect, leading to prolonged blood retention and improved bioavailabilities at targeted cells. Furthermore, the dynamic surroundings shifted towards relatively positive charges in the tumor microenvironment (pH 6.8). As a result, the nanoparticles were more likely to be taken up by tumors due to their electrostatic affinities towards polyanionic cytomembranes. Eventually, the internalized mRNA nanomedicine transformed responsive to the surrounding microenvironment into highly positive charges within acidic endolysosomes (pH 5.0), exerting explosive disruptive potencies on the endolysosomal structures, thus facilitating translocation of mRNA from the digestive endolysosomes into the targeted cytosol. Notably, the dynamic surroundings also reduced the immunogenicity of naked mRNA due to their stealthy properties and rapid endolysosomal translocation functions. In summary, our proposed unique triple-transformable dynamic surface chemistry provided an intriguing delivery scenario that overcomes sequential biological barriers, contributing to efficient expression of the encapsulated mRNA at targeted 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 Elsevier Ltd. All rights reserved.)

Focal adhesion kinase (FAK) is considered as a pivotal intracellular non-receptor tyrosine kinase, and has garnered significant attention as a promising target for anticancer drug development. As of early 2024, a total of 12 drugs targeting FAK have been approved for clinical or preclinical studies worldwide, including three PROTAC degraders. In recent three years (2021-2023), significant progress has been made in designing targeted FAK anticancer agents, including the development of a novel benzenesulfofurazan type NO-releasing FAK inhibitor and the first-in-class dual-target inhibitors simultaneously targeting FAK and HDACs. Given the pivotal role of FAK in the discovery of anticancer drugs, as well as the notable advancements achieved in FAK inhibitors and PROTAC degraders in recent years, this review is underbaked to present a comprehensive overview of the function and structure of FAK. Additionally, the latest findings on the inhibitors and PROTAC degraders of FAK from the past three years, along with their optimization strategies and anticancer activities, were summarized, which might help to provide novel insights for the development of novel targeted FAK agents with promising anticancer potential and favorable pharmacological profiles., Competing Interests: Declaration of competing interest There is no conflict of interest about this article., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Unveiling the intricate relationship between cancer and Golgi viscosity remains an arduous endeavor, primarily due to the lack of Golgi-specific fluorescent probes tailored for viscosity measurement. Considering this formidable obstacle, we have triumphed over the challenge by devising a bespoke Golgi-specific viscosity probe, aptly named GOL-V. This ingenious innovation comprises the viscosity rotor BODIPY intricately tethered to the Golgi-targeting moiety benzsulfamide. GOL-V exhibits remarkable sensitivity to fluctuations in viscosity, the fluorescence intensity of GOL-V increased 114-fold when the viscosity value was increased from 2.63 to 937.28 cP. Owing to its remarkable capacity to suppress the TICT state under conditions of heightened viscosity. Moreover, its efficacy in sensitively monitoring Golgi viscosity alterations within living cells is also very significant. Astonishingly, our endeavors have culminated in not only the visualization of Golgi viscosity at the cellular and tissue levels but also in the clinical tissue samples procured from cancer patients. Harnessing the prowess of GOL-V, we have successfully demonstrated that Golgi viscosity could serve as a discerning marker for detecting the presence of cancer. The convergence of these exceptional attributes firmly establishes GOL-V as an immensely potent instrument, holding immense potential in the realm of cancer diagnosis., 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. Published by Elsevier B.V.)

Cancer, a prevalent and complex disease, presents a significant challenge to the medical community. It is characterized by irregular cell differentiation, excessive proliferation, uncontrolled growth, invasion of nearby tissues, and spread to distant organs. Its progression involves a complex interplay of several elements and processes. Extracellular vesicles (EVs) serve as critical intermediaries in intercellular communication, transporting critical molecules such as lipids, RNA, membrane, and cytoplasmic proteins between cells. They significantly contribute to the progression, development, and dissemination of primary tumors by facilitating the exchange of information and transmitting signals that regulate tumor growth and metastasis. However, EVs do not have a singular impact on cancer; instead, they play a multifaceted dual role. Under specific circumstances, they can impede tumor growth and influence cancer by delivering oncogenic factors or triggering an immune response. Furthermore, EVs from different sources demonstrate distinct advantages in inhibiting cancer. This research examines the biological characteristics of EVs and their involvement in cancer development to establish a theoretical foundation for better understanding the connection between EVs and cancer. Here, we discuss the potential of EVs from various sources in cancer therapy, as well as the current status and future prospects of engineered EVs in developing more effective cancer treatments., (© 2024. The Author(s).)

The suppressive tumour microenvironment significantly hinders the efficacy of immunotherapy in treating solid tumors. In this context, stromal cells, such as tumour-associated fibroblasts, undergo changes that include an increase in the number and function of immunosuppressive cells. Adenosine, a factor that promotes tumour growth, is produced from ATP breakdown and is markedly elevated in the tumour microenvironment. It acts through specific binding to adenosine receptors, with A2A and A2B adenosine receptor being primary drivers of immunosuppression. This paper presents the roles of various adenosine receptors in different tumour microenvironments. This review focus on the function of adenosine receptors in the stromal cells and non-cellular components of the tumour microenvironment. Additionally, we summarize and discuss recent advances and potential trends in using adenosine receptor antagonists combined with immunotherapy., 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 Han, Dong, Hu, Wang and Wang.)

The zinc finger protein of the cerebellum (ZIC) family comprises five members (ZIC1-5), homologous with the odd-paired (OPA) gene in Drosophila melanogila. These transcription factors contain five Cys2His zinc finger domains, constituting one of the most abundant transcription factor families in human cells. ZIC proteins significantly contribute to transcriptional regulation and chromatin remodeling. As a member of the ZIC family, ZIC5 is essential for animal growth and development. Numerous studies have investigated the connection between ZIC proteins and cancer as well as tumor metastases in recent years. Many studies have found that within tumor tissues, the transcription and translation processes increase the expression of ZIC5 which is linked to tumor aggressiveness. This review aims to provide an objective summary of the impact of ZIC5 on tumor metastasis and consider the potential application of ZIC5 targets in both tumor therapy and the early detection of cancer., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Radiotherapy is an important treatment for many unresectable advanced malignant tumors, and radiotherapy-associated inflammatory reactions to radiation and other toxic side effects are significant reasons which reduce the quality of life and survival of patients. FLASH-radiotherapy (FLASH-RT), a prominent topic in recent radiation therapy research, is an ultra-high dose rate treatment known for significantly reducing therapy time while effectively targeting tumors. This approach minimizes radiation side effects on at-risk organs and maximally protects surrounding healthy tissues. Despite decades of preclinical exploration and some notable achievements, the mechanisms behind FLASH effects remain debated. Standardization is still required for the type of FLASH-RT rays and dose patterns. This review addresses the current state of FLASH-RT research, summarizing the biological mechanisms behind the FLASH effect. Additionally, it examines the impact of FLASH-RT on immune cells, cytokines, and the tumor immune microenvironment. Lastly, this review will discuss beam characteristics, potential clinical applications, and the relevance and applicability of FLASH-RT in treating advanced cancers.

Tumorigenesis is a multistep process, with oncogenic mutations in a normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic mutations and clonal expansion in normal tissues, their transformation into cancer remains a rare event, indicating the presence of additional driver events for progression to an irreversible, highly heterogeneous, and invasive lesion. Recently, researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution, independently of inducing mutations. Additionally, clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors. However, the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood. In this review, we summarize the genetic, epigenetic, and external driver events, and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution. A deeper understanding of the earliest molecular events holds promise for translational applications, predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation., (© 2024. The Author(s).)

In recent decades, many reports have been published on the composition and function of the tumor microenvironment (TME), among which cancer-associated fibroblasts (CAFs) have received much attention. CAFs have different degrees of heterogeneity in terms of their origin, phenotype, and function and can be divided into different subpopulations. These subgroups may play different roles in the occurrence and development of tumors. In addition, CAFs are closely associated with tumor immunity and have been found to regulate immune cell activity and to suppress the tumor immune response. In this review, we systematize the heterogeneity and characteristics of CAFs, discuss how specific CAF subgroups contribute to cancer progression by inducing an immunosuppressive microenvironment, and finally, we examine the future clinical applications of CAF subgroups., (© 2024. The Author(s).)