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Neuroblastoma is the most common extracranial malignant tumor of childhood, accounting for 15% of all pediatric cancer deaths. Despite significant advances in our understanding of neuroblastoma biology, five-year survival rates for high-risk disease remain less than 50%, highlighting the importance of identifying novel therapeutic targets to combat the disease. MYCN amplification is the most frequent and predictive molecular aberration correlating with poor outcome in neuroblastoma. N-Myc is a short-lived protein primarily due to its rapid proteasomal degradation, a potentially exploitable vulnerability in neuroblastoma. AF1q is an oncoprotein with established roles in leukemia and solid tumor progression. It is normally expressed in brain and sympathetic neurons and has been postulated to play a part in neural differentiation. However, no role for AF1q in tumors of neural origin has been reported. In this study, we found AF1q to be a universal marker of neuroblastoma tumors. Silencing AF1q in neuroblastoma cells caused proteasomal degradation of N-Myc through Ras/ERK and AKT/GSK3β pathways, activated p53 and blocked cell cycle progression, culminating in cell death via the intrinsic apoptotic pathway. Moreover, silencing AF1q attenuated neuroblastoma tumorigenicity in vivo signifying AF1qs importance in neuroblastoma oncogenesis. Our findings reveal AF1q to be a novel regulator of N-Myc and potential therapeutic target in neuroblastoma.

Osteosarcoma(OS) is a highly aggressive bone cancer for which treatment has remained essentially unchanged for decades. Although OS is characterized by extensive genomic heterogeneity and instability, RB1 and TP53 have been shown to be the most commonly inactivated tumor suppressors in OS. We previously generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which largely recapitulates human OS with nearly complete penetrance. SKP2 is a repression target of pRb and serves as a substrate recruiting subunit of the SCFSKP2 complex. In addition, SKP2 plays a central role in regulating the cell cycle by ubiquitinating and promoting the degradation of p27. We previously reported the DKOAA transgenic model, which harbored a knock-in mutation in p27 that impaired its binding to SKP2. Here, we generated a novel p53-Rb1-SKP2 triple-knockout model (TKO) to examine SKP2 function and its potential as a therapeutic target in OS. First, we observed that OS tumorigenesis was significantly delayed in TKO mice and their overall survival was markedly improved. In addition, the loss of SKP2 also promoted an apoptotic microenvironment and reduced the stemness of DKO tumors. Furthermore, we found that small-molecule inhibitors of SKP2 exhibited anti-tumor activities in vivo and in OS organoids as well as synergistic effects when combined with a standard chemotherapeutic agent. Taken together, our results suggest that SKP2 inhibitors may reduce the stemness plasticity of OS and should be leveraged as next-generation adjuvants in this cancer.

The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYChigh but not MYClow cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYChigh murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous MYC-transgenic HCC model and inhibits tumor growth in HCC patient-derived xenografts. XPO1 expression is associated with poor prognosis only in HCC patients with high MYC activity. We infer that MYC may generally regulate and require altered expression of nucleocytoplasmic transport genes for tumorigenesis.

TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression.

Background: The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study investigates microbial communities in OPMDs. Materials and methods: Oral biopsies from19 oral leukoplakia (OLK) patients, 19 proliferative verrucous leukoplakia (PVL) patients, 19 oral lichen planus (OLP) patients, and 19 oral lichenoid lesions (OLL) patients were obtained. 15 SCC specimens were also collected from PVL patients. Healthy individuals served as controls, and DNA was extracted from their paraffin-embedded tissues. 2bRAD-M sequencing generated taxonomic profiles. Alpha and beta diversity analyses, along with Linear Discriminant Analysis effect size analysis, were conducted. Results: Our results showed the microbial richness and diversity were significantly different among groups, with PVL-SCC resembling controls, while OLK exhibited the highest richness. Each disease group displayed unique microbial compositions, with distinct dominant bacterial species. Noteworthy alterations during PVL-SCC progression included a decline in Fusobacterium periodonticum and an elevation in Prevotella oris. Conclusions: Different disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating evidence has supported that gut microbiota and metabolite profiles play indispensable roles in the pathogenesis of colorectal cancer (CRC), which ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide. However, alterations in tumoral or circulating microbiomes in CRC remain incompletely understood. It has been well-documented that tissue or serum microbiomes with low microbial biomass could be screened by use of 2bRAD sequencing for microbiome (2bRAD-M) at the species resolution. Methods: In order to validate the microbial biomarkers distinguishing CRC and the variations in microorganisms present in serum and tumors, we performed 2bRAD-M to characterize the microbiomes in serum and cancer tissues of CRC patients with and without lymph node or liver metastasis. Results: The composition of dominated microbiota in serum was different from that of tissue samples, while the microbial community composition of tumors was similar to that of the tumor-adjacent tissues. The analysis of α-diversity and β-diversity has revealed notable variations in serum microbiota diversities in CRC patients, particularly those with liver metastasis. Multiple CRC-specific microbial species, such as Moraxella A cinereus, Flavobacterium sp001800905, and Acinetobacter albensis, were identified in serum. Complicated functions and KEGG pathways were also confirmed in CRC according to the metastasis status. Discussion: This study has found significant alterations in the microbial compositions and diversities in CRC and CRC-specific microbial species in both circulation and cancer tissues, which may serve as promising biomarkers for the screening, diagnosis and prognosis prediction of CRC. In particular, CRC-specific bacterial taxa are promising markers, holding transformative potentials in establishing personalized screening and risk stratification, refining much earlier non-invasive diagnostic approaches, and enhancing diagnostic sensitivity. [ABSTRACT FROM AUTHOR]

Cancer therapy is facing increasingly significant challenges, marked by a wide range of techniques and research efforts centered around somatic mutations, precision oncology, and the vast amount of big data. Despite this abundance of information, the quest to cure cancer often seems more elusive, with the "war on cancer" yet to deliver a definitive victory. A particularly pressing issue is the development of tumor treatment resistance, highlighting the urgent need for innovative approaches. Evolutionary, Quantum Biology and System Biology offer a promising framework for advancing experimental cancer research. By integrating theoretical studies, translational methods, and flexible multidisciplinary clinical research, there's potential to enhance current treatment strategies and improve outcomes for cancer patients. Establishing stronger links between evolutionary, quantum, entropy and chaos principles and oncology could lead to more effective treatments that leverage an understanding of the tumor's evolutionary dynamics, paving the way for novel methods to control and mitigate cancer. Achieving these objectives necessitates a commitment to multidisciplinary and interprofessional collaboration at the heart of both research and clinical endeavors in oncology. This entails dismantling silos between disciplines, encouraging open communication and data sharing, and integrating diverse viewpoints and expertise from the outset of research projects. Being receptive to new scientific discoveries and responsive to how patients react to treatments is also crucial. Such strategies are key to keeping the field of oncology at the forefront of effective cancer management, ensuring patients receive the most personalized and effective care. Ultimately, this approach aims to push the boundaries of cancer understanding, treating it as a manageable chronic condition, aiming to extend life expectancy and enhance patient quality of life. [ABSTRACT FROM AUTHOR]

Calcium is a fundamental and integrative element and helps to ensure optimal health by regulating various physiological and pathological processes. While there is substantiated evidence confirming the beneficial effects of calcium in the treatment, management, and prevention of various health conditions, including cancer, conflicting studies are imperative to acknowledge the potential negative role of calcium supplementation. The studies on calcium supplementation showed that a specific dose can help in the maintenance of good human health, and in the control of different types of diseases, including cancer. Calcium alone and when combined with vitamin D, emerges as a promising therapeutic option for efficiently managing cancer growth, when used with chemotherapy. Combination therapy is considered a more effective approach for treating advanced types of colorectal cancer. Nevertheless, several challenges drastically influence the treatment of cancer, such as individual discrepancy, drug resistance, and stage of cancer, among others. Henceforth, novel preventive, reliable therapeutic modalities are essential to control and reduce the incidence and mortality of colorectal cancer (CRC). The calcium-sensing receptor (CaSR) plays a pivotal role in calcium homeostasis, metabolism, and regulation of oncogenesis. Numerous studies have underscored the potential of CaSR, a G protein-coupled receptor, as a potential biomarker and target for colorectal cancer prevention and treatment. The multifaceted involvement of CaSR in anti-inflammatory and anti-carcinogenic processes paves the way for its utilization in the diagnosis and management of colorectal cancer. The current review highlights the important role of supplemental calcium in overall health and disease, along with the exploration of intricate mechanisms of CaSR pathways in the management and prevention of colorectal cancer. [ABSTRACT FROM AUTHOR]

Aim: To determine the association of the presence of diabetes and, among persons with diabetes, the age at type 2 diabetes mellitus (T2DM) onset, BMI and the interactive effect with the subsequent thyroid cancer risk. Materials and Methods: We conducted a population register‐based longitudinal cohort study in Shanghai, including 428 568 persons with new‐onset T2DM matched with the general population. The risk of thyroid cancer among subgroups was calculated based on standardized incidence ratio (SIR), hazard ratio (HR) and Cox proportional hazards models. Results: In total, 1142 thyroid cancer cases were identified during 8 years of follow‐up, with an incidence rate of 59.01/100 000 person‐years and a higher risk (SIR = 1.21) compared with the general population. The earlier age at T2DM onset and higher BMI were associated with an increasing risk of thyroid cancer independently (onset age <50, SIR: 1.46; BMI ≥30.0 kg/m2, SIR: 1.93), with the highest risk in patients with both BMI ≥30.0 kg/m2 and onset age <50 years (SIR = 3.91, HR = 3.04). Among patients with T2DM onset age <60 years, SIR increased with higher BMI, while there were no trends when onset age ≥60 years. Among patients with BMI ≥25.0 kg/m2, SIR increased with an earlier onset age, whereas no trends were shown in the BMI <24.9 kg/m2 groups. Obese (BMI ≥30.0 kg/m2) patients had a significantly higher HR of thyroid cancer only when T2DM onset age <60 years. Conclusions: Both earlier age of T2DM onset (<50 years) and higher BMI (≥30 kg/m2) contributed to the higher risk of thyroid cancer. Patients with young‐onset T2DM and obesity are considered more vulnerable to thyroid cancer development. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate all studies which used the micronucleus assay using oral cells in the attempt to understand whether such technique is efficient in evaluating genotoxicity in gas station attendants. Full manuscripts from 16 studies were carefully selected by the authors. Our results demonstrate that continuous exposure to derivatives of petroleum may lead to genotoxic effects since all studies demonstrated positive findings (16 out of 16) and 11 of them had a strong or moderate final rating. In summary, our results reveal that gas station attendants are occupationally exposed to genotoxic agents and that the micronucleus assay in oral mucosa is indeed an effective method to evaluate genotoxicity in this specific case. Such findings are very important for protecting these professionals who are continuously exposed to chemicals for long periods. [ABSTRACT FROM AUTHOR]

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/β-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice. [ABSTRACT FROM AUTHOR]

One of the most extensively used herbal medicines is chrysin, a naturally occurring flavone commonly detected in several natural products, including propolis and honey. Due to its various biological properties, such as antioxidant, anti-estrogenic, anti-inflammatory, anti-allergic, antibacterial and anticancer activities, chrysin has emerged as the leading contender for health benefits. Amongst the several pharmacological effects exhibited by chrysin, its anticancer activity is the most attractive. Several studies have demonstrated that chrysin suppresses tumor progression in cell lines and animal models by inducing apoptosis, disrupting the cell cycle and inhibiting migration without generating toxicity or undesired side-effects in normal cells. Furthermore, chrysin also inhibits multi-drug resistant proteins and is effective in combination therapy. The present review comprehensively discusses the research developments in the understanding of the potential of chrysin as a potent anticancer agent achieved by modulating various cell targets and signaling pathways involved in inflammation, cell survival, apoptosis, growth, angiogenesis, invasion and metastasis. [ABSTRACT FROM AUTHOR]

The present study conducted an extensive review of the literature that describes the molecular pathogenesis of cancer and glioblastoma multiforme (GBM), exploring physiological adaptation resulting from exercise training in the broader context of cancer and brain tumors, with a specific emphasis on GBM, aiming to discern the implications of exercise in improving the quality of life (QoL) of affecting patients. GBM is the predominant aggressive malignant primary brain tumor with a high mortality rate. GBM involves multiple pathways that can be targeted by exercise training. Exercise has shown its value in various other cancer types and offers a promising approach for GBM. Exercise training is regarded as a safe and feasible adjunctive treatment to improve the QoL of patients with brain tumors, including GBM. Nevertheless, further research is required in order to fully elucidate the mechanisms through which exercise affects cellular processes impacted by cancer and its treatments, with a specific focus on GBM. While exercise training guidelines have been established for cancer patients in general, there is currently a lack of specific guidelines tailored to patients with GBM. Clear guidelines are essential to assist clinicians in determining the most appropriate exercise type, intensity and frequency for patients to optimize their rehabilitation process. [ABSTRACT FROM AUTHOR]

The present article assesses, for the first time, the level of heavy metal pollution, determines possible sources and evaluates the health risks associated with groundwater in the Angads plain in Morocco, by employing a combination of tools including indices, statistical multivariate techniques and models for health risk assessment. The findings revealed that the concentrations of several heavy metals (95.83% for As and 41.66% for Pb) were above the WHO limit values. The heavy metal pollution index (HPI) and the heavy metal evaluation index (HEI) revealed that all samples were fit for consumption. Health risks revealed that the hazard index (HI) values for dermal exposure were below the limit, while for oral exposure, 95.83% of samples were above the limit. In addition, the carcinogenic risk (CR) results revealed that there is a possibility of cancer development due to lifetime exposure to this groundwater. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the 3rd most common cancer in the world and colonic carcinogenesis is a multifactorial disease that involves environmental and genetic factors. Gut microbiota plays a critical role in the regulation of intestinal homeostasis. Increasing evidence shows that the gut microbiome plays a role in CRC development and may be a biomarker for early diagnosis. Objective: This study aimed to determine the clinical prognostic significance of gut microbiota in CRC patients in the Turkish population by metagenomic analysis and to determine the microbial composition in tumor tissue biopsy samples. Methods: Tissue biopsies were taken from the participants with sterile forceps during colonoscopy and stored at -80 °C. Then, DNA isolation was performed from the tissue samples and the V3-V4 region of the 16 S rRNA gene was sequenced on the Illumina MiSeq platform. Quality control of the obtained sequence data was performed. Operational taxonomic units (OTUs) were classified according to the Greengenes database. Alpha diversity (Shannon index) and beta diversity (Bray-Curtis distance) analyses were performed. The most common bacterial species in CRC patients and healthy controls were determined and whether there were statistically significant differences between the groups was tested. Results: A total of 40 individuals, 13 CRC patients and 20 healthy control individuals were included in our metagenomic study. The mean age of the patients was 64.83 and BMI was 25.85. In CRC patients, the level of Bacteroidetes at the phylum taxonomy was significantly increased (p = 0.04), the level of Clostridia at the class taxonomy was increased (p = 0.23), and the level of Enterococcus at the genus taxonomy was significantly increased (p = 0.01). When CRC patients were compared with the control group, significant increases were detected in the species of Gemmiger formicilis (p = 0.15), Prevotella copri (p = 0.02) and Ruminococcus bromii (p = 0.001) at the species taxonomy. Conclusions: Metagenomic analysis of intestinal microbiota composition in CRC patients provides important data for determining the treatment options for these patients. The results of this study suggest that it may be beneficial in terms of early diagnosis, poor prognosis and survival rates in CRC patients. In addition, this metagenomic study is the first study on the colon microbiome associated with CRC mucosa in the Turkish population. [ABSTRACT FROM AUTHOR]

Thyroid hormone has been shown to have both tumor-promoting and tumor-suppressing actions, which has led to significant debate over its involvement in the development of cancer. Proliferation, apoptosis, invasiveness, and angiogenesis are all aspects of cancer that are affected by the thyroid hormones T3 and T4, according to research conducted in animal models and in vitro experiments. The effects of thyroid hormones on cancer cells are mediated by many non-genomic mechanisms, one of which involves the activation of the plasma membrane receptor integrin αvβ3. Typically, abnormal amounts of thyroid hormones are linked to a higher occurrence of cancer. Both benign and malignant thyroid disorders were found to be associated with an increased risk of extra-thyroidal malignancies, specifically colon, breast, prostate, melanoma, and lung cancers. The purpose of this review was to shed light on this link to define which types of cancer are sensitive to thyroid hormones and, as a result, are anticipated to respond favorably to treatment of the thyroid hormone axis. [ABSTRACT FROM AUTHOR]

Despite advances in treatment strategies, breast cancer (BC) remains one of the most prevalent cancers worldwide. Recent studies implicate the gut microbiome as a potential risk factor for BC development. Alterations in gut microbial diversity resulting in dysbiosis have been linked to breast carcinogenesis by modulating host immune responses and inflammatory pathways, favoring tumorigenesis and progression. Moreover, gut microbiota populations are different between women with BC vs those that are cancer free, further implicating the role of the gut microbiome in cancer development. This alteration in gut microbiota is also associated with changes in estrogen metabolism, which strongly correlates with BC development. Gut microbiota that express the enzyme β-glucuronidase (GUS) may increase estrogen bioavailability by deconjugating estrogen-glucuronide moieties enabling reabsorption into circulation. Increased circulating estrogens may, in turn, drive estrogen receptor–positive BC. GUS-expressing microbiota also affect cancer therapy efficacy and toxicity by modifying glucuronide-conjugated drug metabolites. Therefore, GUS inhibitors have emerged as a potential antitumor treatment. However, the effectiveness of GUS inhibitors is still exploratory. Further studies are needed to determine how oral endocrine-targeting therapies may influence or be influenced by the microbiota and how that may affect carcinogenesis initiation and tumor recurrence. [ABSTRACT FROM AUTHOR]

The article presents a case study of a fair-skinned, elderly woman experiencing a sudden increase in skin malignancies after a long period of stability. Topics discussed include the management of skin lesions through shave and curettage, the impact of ruxolitinib on skin cancer progression, and factors contributing to the rapid rise in skin malignancies.

Hepatitis C virus (HCV) chronically infects approximately 170 million people worldwide and is a known etiological agent of hepatocellular carcinoma (HCC). The molecular mechanisms of HCV-mediated carcinogenesis are not fully understood. This review article focuses on the oncogenic potential of NS3, a viral protein with transformative effects on cells, although the precise mechanisms remain elusive. Unlike the more extensively studied Core and NS5A proteins, NS3's roles in cancer development are less defined but critical. Research indicates that NS3 is implicated in several carcinogenic processes such as proliferative signaling, cell death resistance, genomic instability and mutations, invasion and metastasis, tumor-related inflammation, immune evasion, and replicative immortality. Understanding the direct impact of viral proteins such as NS3 on cellular transformation is crucial for elucidating HCV's role in HCC development. Overall, this review sheds light on the molecular mechanisms used by NS3 to contribute to hepatocarcinogenesis, and highlights its significance in the context of HCV-associated HCC, underscoring the need for further investigation into its specific molecular and cellular actions. [ABSTRACT FROM AUTHOR]

The placenta, a pivotal organ in mammalian reproduction, allows nutrient exchange and hormonal signaling between the mother and the developing fetus. Understanding its molecular intricacies is essential for deciphering normal embryonic development and pathological conditions such as tumorigenesis. Here, we explore the multifaceted role of the tumor suppressor BRCA1-associated protein 1 (BAP1) in cancer and placentation. Initially recognized for its tumor-suppressive properties, BAP1 has emerged as a key regulator at the intersection of tumorigenesis and placental development. BAP1 influences crucial cellular processes such as cell death, proliferation, metabolism, and response to hypoxic conditions. By integrating insights from tumor and developmental biology, we illuminate the complex molecular pathways orchestrated by BAP1. This perspective highlights BAP1's significant impact on both cancer and placental development, and suggests novel therapeutic strategies that could improve outcomes for pregnancy disorders and cancer. This perspective explores the dual role of the tumor suppressor BAP1 in placental development and cancer. By integrating insights from tumor and developmental biology, the study offers new therapeutic targets for pregnancy disorders and cancer. [ABSTRACT FROM AUTHOR]

Quinazolinone derivatives have garnered attention for their diverse biological activities, including anticancer properties. This review combines findings from 2018 to 2024, focusing on the impact of quinazolinones on cancer cells, tubulin formation, and EGFR/PI3 K pathways. By unraveling the intricacies of structure‐activity relationships, this review endeavors to provide guidance for researchers in identifying promising avenues for the development of cancer treatments. Although in vitro studies underscore significant potential, it is imperative that future research prioritizes pre‐clinical investigations to seamlessly traverse the transitional phase towards clinical applications, thereby propelling the advancement of quinazolinone‐based cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Patients' expectations regarding medical information in advanced stages of cancer are still poorly understood. Tailoring information to advanced cancer patients is a subtle task. We developed a question prompt list (QPL) that serves as a patient-oncologist communication aid in France. Methods: A four-step sequential mixed method involving patients with luminal B/triple-negative metastatic breast cancer or metastatic uveal melanoma (N = 110) and patients' partners, oncologists, and researchers (N = 18) was used. In-depth interviews and questionnaires focused on the information needed at the disclosure of metastasis or resistance to treatment (step 1), the formulation of questions and procedures for use in oncology visits (steps 2 and 3), and the acceptability of the final tool (stage 4). Results: The initial version of the QPL consists of 17 questions covering 5 themes (disease, current treatment, other options, living with cancer, prognosis). In step 2, 13 questions were added, 2 were merged, and 5 were deleted; a short form (4 questions) and recommendations for clinical use were proposed. In step 3, 2 questions were merged, and 6 were deleted. Four oncologists (27% of the target population) took part in step 4, and the QPL was discussed with 20 patients, revealing a positive appraisal. Conclusion: We provide a rigorously developed, relevant, concise, and acceptable question prompt list for clinical application in the advanced cancer care setting in France. Further research needs to assess whether this tool actually facilitates oncologist–patient communication and improves satisfaction with care and health outcomes. Trial registration: The study is listed on ClinicalTrials.gov (NCT04118062) and registered under identification n° IRRID "International Registered Report Identifier": DERR1-10.2196/26414. [ABSTRACT FROM AUTHOR]

Pregnancy‐associated breast cancer has been increasing. In this study, we analyzed patients with breast cancer that occurred during pregnancy (PrBC) and compared their genetic profiles with those of patients with breast cancer that did not occur during pregnancy, within 1 year after childbirth nor during lactation (non‐PrBC). We performed gene expression analyses of patients with PrBC and non‐PrBC using microarrays and qRT‐PCR. Microarray analysis showed that 355 genes were upregulated in the luminal‐type PrBC group compared to those in the non‐PrBC group. The C‐X‐C motif chemokine ligand 13 (CXCL13) gene was the most upregulated in the PrBC group compared to that in the non‐PrBC group, especially in the luminal A‐type (p = 0.016). This result was corroborated by the qRT‐PCR analysis of microdissected cancer cells (p < 0.001). A negative correlation was observed between CXCL13 and estrogen receptor 1 (ESR1) mRNA expression levels in luminal A‐type breast carcinoma (p < 0.001). Our results provide clues for a better understanding of breast cancer pathogenesis during pregnancy. [ABSTRACT FROM AUTHOR]

Activated Wnt/β-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of β-catenin in liver cancer. SLC13A3 expression is elevated in human liver cancer samples with gain of function (GOF) mutant CTNNB1, the gene encoding β-catenin. Activation of β-catenin up-regulates SLC13A3, leading to intracellular accumulation of endogenous SLC13A3 substrates. SLC13A3 is identified as a low-affinity transporter for glutathione (GSH). Silencing of SLC13A3 downregulates the leucine transporter SLC7A5 via c-MYC signaling, leading to leucine depletion and mTOR inactivation. Furthermore, silencing of SLC13A3 depletes GSH and induces autophagic ferroptosis in β-catenin-activated liver cancer cells. Importantly, both genetic inhibition of SLC13A3 and a small molecule SLC13A3 inhibitor suppress β-catenin-driven hepatocarcinogenesis in mice. Altogether, our study suggests that SLC13A3 could be a promising therapeutic target for treating human liver cancers with GOF CTNNB1 mutations. The therapeutic approaches directly targeting activated β-catenin in liver cancers are restricted by toxicities. Here the authors identify that the solute carrier transporter SLC13A3 is upregulated by activation of β-catenin and silencing of SLC13A3 induces ferroptosis, which could be exploited as a therapeutic opportunity in β-catenin-driven liver cancers. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression. [ABSTRACT FROM AUTHOR]

Introduction: The thyroid cancer has the ninth larger incidence of cancer in the world. Investigations related to the exposure to metals have become important due to the sensibility of the thyroid gland to them. Studies reveal that carcinogenic progressions are associated to the deficiency of the essential trace elements. In this context, the zinc is highlighted, essential for the metabolism of the thyroidal hormone and has a potential relation with the pathogenesis of the thyroid cancer. The objective of this systematic review and meta-analysis is to evaluate the low serum zinc as a risk factor for thyroid cancer in adults. Methods and analysis: PubMed/MEDLINE, Scopus, Embase and LILACS databases will be searched for observational studies investigating the low serum zinc as a risk factor for thyroid cancer in adults. No language or publication period restrictions will be imposed. The primary outcome will be that the low serum zinc is a risk factor for thyroid cancer. Three independent reviewers will select the studies and extract data from the original publications. The risk-of-bias will be assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data synthesis will be performed using the R software (V.4.3.1) and to assess heterogeneity, we will compute the I2 statistic and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence. Prospero registration number: International Prospective Register of Systematic Reviews (PROSPERO) CRD42023463747. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among the highest in the world. Cancer development is associated with aberrant signaling pathways. Autophagy is a process of cell self-digestion that maintains the intracellular environment and has a bidirectional regulatory role in cancer. Apoptosis is one of the important death programs in cancer cells and is able to inhibit cancer development. Studies have shown that a variety of substances can regulate autophagy and apoptosis in colorectal cancer cells through signaling pathways, and participate in the regulation of autophagy on apoptosis. In this paper, we focus on the relevant research on autophagy in colorectal cancer cells based on the involvement of related signaling pathways in the regulation of apoptosis in order to provide new research ideas and therapeutic directions for the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is one of the most common gynecologic cancers. In recent years, research has focused on the genetic characteristics of the tumors to detail their prognosis and tailor therapy. In the case of EC, genetic mutations have been shown to underlie their formation. It is very important to know the mechanisms of EC formation related to mutations induced by estrogen, among other things. Noncoding RNAs (ncRNAs), composed of nucleotide transcripts with very low protein-coding capacity, are proving to be important. Their expression patterns in many malignancies can inhibit tumor formation and progression. They also regulate protein coding at the epigenetic, transcriptional, and posttranscriptional levels. MicroRNAs (miRNAs), several varieties of which are associated with normal endometrium as well as its tumor, also play a particularly important role in gene expression. MiRNAs and long noncoding RNAs (lncRNAs) affect many pathways in EC tissues and play important roles in cancer development, invasion, and metastasis, as well as resistance to anticancer drugs through mechanisms such as suppression of apoptosis and progression of cancer stem cells. It is also worth noting that miRNAs are highly precise, sensitive, and robust, making them potential markers for diagnosing gynecologic cancers and their progression. Unfortunately, as the incidence of EC increases, treatment becomes challenging and is limited to invasive tools. The prospect of using microRNAs as potential candidates for diagnostic and therapeutic use in EC seems promising. Exosomes are extracellular vesicles that are released from many types of cells, including cancer cells. They contain proteins, DNA, and various types of RNA, such as miRNAs. The noncoding RNA components of exosomes vary widely, depending on the physiology of the tumor tissue and the cells from which they originate. Exosomes contain both DNA and RNA and have communication functions between cells. Exosomal miRNAs mediate communication between EC cells, tumor-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and play a key role in tumor cell proliferation and tumor microenvironment formation. Oncogenes carried by tumor exosomes induce malignant transformation of target cells. During the synthesis of exosomes, various factors, such as genetic and proteomic data are upregulated. Thus, they are considered an interesting therapeutic target for the diagnosis and prognosis of endometrial cancer by analyzing biomarkers contained in exosomes. Expression of miRNAs, particularly miR-15a-5p, was elevated in exosomes derived from the plasma of EC patients. This may suggest the important utility of this biomarker in the diagnosis of EC. In recent years, researchers have become interested in the topic of prognostic markers for EC, as there are still too few identified markers to support the limited treatment of endometrial cancer. Further research into the effects of ncRNAs and exosomes on EC may allow for cancer treatment breakthroughs. [ABSTRACT FROM AUTHOR]

Background: Chromosome stability is crucial for homeostasis of pluripotent stem cells (PSCs) and early-stage embryonic development. Chromosomal defects may raise carcinogenic risks in regenerative medicine when using PSCs as original materials. However, the detailed mechanism regarding PSCs chromosome stability maintenance is not fully understood. Methods: Mouse embryonic stem cells (line D3) and human embryonic stem cells (line H9) were cultured under standard conditions. To confirm the loading of RetSat protein on mitotic chromosomes of PSCs, immunostaining was performed in PSCs spontaneous differentiation assay and iPSC reprogramming assay from mouse embryonic fibroblasts (MEFs), respectively. In addition, qPCR, immunoprecipitation, LC-MS/MS and immunoblotting were used to study the expression of RetSat, and interactions of RetSat with cohesin/condensin components. RNA sequencing and teratoma formation assay was conducted to evaluate the carcinogenic risk of mouse embryonic stem cells with RetSat deletion. Results: We reported a PSC high-expressing gene, RetSat, plays key roles in chromosome stabilization. We identified RetSat protein localizing onto mitotic chromosomes specifically in stemness positive cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We found dramatic chromosome instability, e.g. chromosome bridging, lagging and interphase micronuclei in mouse and human ESCs when down regulating RetSat. RetSat knock-out mouse ESCs upregulated cancer associated gene pathways, and displayed higher tumorigenic capacities in teratoma formation assay. Mechanistically, we confirmed that RetSat interacts with cohesin/condensin components Smc1a and Nudcd2. RetSat deletion impaired the chromosome loading dosage of Smc1a, Smc3 and Nudcd2. Conclusions: In summary, we reported RetSat to be a key stabilizer of chromosome condensation in pluripotent stem cells. This highlights the crucial roles of RetSat in early-stage embryonic development, and potential value of RetSat as an effective biomarker for assessing the quality of pluripotent stem cells. [ABSTRACT FROM AUTHOR]

Rational: Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial "field" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases). Methods: Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot. Results: (a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs. Conclusions: These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Recent advances in genomic research have increasingly focused on the fat massand obesity-associated (FTO) gene due to its notable correlation with obesity. Initially explored for its contribution to increased body weight, FTO was later discovered to function as an m6A demethylase. This pivotal role enhances our understanding of its broader implications across various pathologies. Epigenetic modifications, such as m6A, have been implicated in gynecological cancers, including ovarian, endometrial, and cervical malignancies. However, the precise mechanisms by which FTO influences the development of gynecological cancers remain largely unknown. This analysis underscores the growing relevance of investigations into the FTO gene in elucidating the mechanisms underlying gynecological cancers and exploring potential therapeutic avenues. [ABSTRACT FROM AUTHOR]

Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers' understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most common brain tumor with the worst prognosis. Temozolomide is the only first-line drug for GBM. Unfortunately, the resistance issue is a classic problem. Therefore, it is essential to develop new drugs to treat GBM. As an oncogene, Skp2 is involved in the pathogenesis of various cancers including GBM. In this study, we investigated the anticancer effect of AAA237 on human glioblastoma cells and its underlying mechanism. Methods: CCK-8 assay was conducted to evaluate IC50 values of AAA237 at 48, and 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) was employed to ascertain the status of Skp2 as an intrinsic target of AAA237 inside the cellular milieu. The EdU-DNA synthesis test, Soft-Agar assay and Matrigel assay were performed to check the suppressive effects of AAA237 on cell growth. To identify the migration and invasion ability of GBM cells, transwell assay was conducted. RT-qPCR and Western Blot were employed to verify the level of BNIP3. The mRFP-GFP-LC3 indicator system was utilized to assess alterations in autophagy flux and investigate the impact of AAA237 on the dynamic fusion process between autophagosomes and lysosomes. To investigate the effect of compound AAA237 on tumor growth in vivo, LN229 cells were injected into the brains of mice in an orthotopic model. Results: AAA237 could inhibit the growth of GBM cells in vitro. AAA237 could bind to Skp2 and inhibit Skp2 expression and the degradation of p21 and p27. In a dose-dependent manner, AAA237 demonstrated the ability to inhibit colony formation, migration, and invasion of GBM cells. AAA237 treatment could upregulate BNIP3 as the hub gene and therefore induce BNIP3-dependent autophagy through the mTOR pathway whereas 3-MA can somewhat reverse this process. In vivo, the administration of AAA237 effectively suppressed the development of glioma tumors with no side effects. Conclusion: Compound AAA237, a novel Skp2 inhibitor, inhibited colony formation, migration and invasion of GBM cells in a dose-dependent manner and time-dependent manner through upregulating BNIP3 as the hub gene and induced BNIP3-dependent autophagy through the mTOR pathway therefore it might be a viable therapeutic drug for the management of GBM. [ABSTRACT FROM AUTHOR]

Lin28A and Lin28B are paralogous RNA‐binding proteins that play fundamental roles in development and cancer by regulating the microRNA family of tumor suppressor Let‐7. Although Lin28A and Lin28B share some functional similarities with Let‐7 inhibitors, they also have distinct expression patterns and biological functions. Increasing evidence indicates that Lin28A and Lin28B differentially impact cancer stem cell properties, epithelial‐mesenchymal transition, metabolic reprogramming, and other hallmarks of cancer. Therefore, it is important to understand the overexpression of Lin28A and Lin28B paralogs in specific cancer contexts. In this review, we summarize the main similarities and differences between Lin28A and Lin28B, their implications in different cellular processes, and their role in different types of cancer. In addition, we provide evidence of other specific targets of each lin28 paralog, as well as the lncRNAs and miRNAs that promote or inhibit its expression, and how this impacts cancer development and progression. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) stands as a significant health threat to women globally, with high-risk human papillomaviruses as major etiologic agents. The DNA damage repair (DDR) protein topoisomerase I (TOP1) has been linked to various cancers, yet its distinct roles and mechanisms in CC are not fully elucidated. Methods: We investigated TOP1 expression in cervical intraepithelial neoplasia (CIN) and CC tissues utilizing qRT-PCR and IHC, correlating findings with patient prognosis. Subsequent knockdown studies were performed in vitro and in vivo to evaluate the influence of TOP1 on tumor growth, DNA repair, and inflammatory responses. Results: TOP1 was highly expressed in CIN and CC, negatively correlating with patient prognosis. Inhibition of TOP1 impeded CC cell growth and disrupted DNA repair. TOP1 was shown to regulate tumor-promoting inflammation and programmed death-ligand 1 (PD-L1) production in a cGAS-dependent manner. HPV oncoproteins E6 and E7 upregulated TOP1 and activated the cGAS-PD-L1 pathway. Conclusions: TOP1 acts as a DNA repair mediator, promoting CC development and immune evasion. Targeting the TOP1-cGAS-PD-L1 axis could be a potential therapeutic strategy for CC. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that physiologically normal skin harbors pervasive mutant clones with cancer drivers. Normal skin has the highest burden of somatic mutations due to persistent ultraviolet exposure throughout life. The mutation burden exponentially increases with age and is further modified by skin site, sun-damage history, and skin phototype. Driver gene profiles in normal skin are similar to those in cutaneous squamous cell carcinoma where NOTCH family, FAT family, and TP53 are consistently reported, while other reported profiles include PPM1D, KMT2D, ASXL1, and RBM10. Normal skin seldom harbors canonical hotspot mutations with therapeutic relevance. The pathologic role of mutant clones with cancer drivers in normal skin is classically considered precursors for skin cancer; however, recent evidence also suggests their putative cancer-protective role. Copy number alterations and other structural variants are rare in normal skin with loss in 9q region encompassing NOTCH1 being the most common. Study methodologies should be carefully designed to obtain an adequate number of cells for sequencing, and a comparable number of cells and read depth across samples. In conclusion, this review provides mutational landscapes of normal skin and discusses their potential implications in the development of skin cancer, highlighting the role of driver genes in early malignant progression. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective observational study recruited 380 patients, 115 with lung cancer and 265 in the control group. Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) were significantly higher in cancer patients than in the control group. The correlation of PLR with the probability of lung cancer differs between men and women. CRP values did not differ according to histological types of lung cancer (p = 0.242) and were not associated with the presence of mutations in EGFR (p = 0.679). CRP values were significantly lower in NSCLC patients with PD-L1 mutations than in those without PD-L1 mutations (22.7 [IQR: 10.4;40.3] vs. 76.7 [IQR: 32.6;140] mg/L, p = 0). Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș involving patients with lung cancer. The parameters analyzed included histopathological type (NSCLC: squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters, and associated comorbidities. Results: A total of 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5.30 versus 2.60, p < 0.001; 217 versus 136, p < 0.001, respectively). NLR and PLR differ between men and women (p = 0.005 and p = 0.056, respectively). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusions: The NLR and PLR values may serve as new predictive biomarkers for the diagnosis of disease in patients with lung cancer, especially those with NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is a complex disease arising from an interplay of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. While most cSCC cases can be treated with surgery, metastatic and locally advanced forms have a significantly worse prognosis and limited treatment options. The high mutational burden in cSCC makes it challenging to identify true driver alterations. Beyond genetics, the tumor microenvironment and its interaction with the immune system play a critical role in cSCC progression, evidenced by differences observed between immunocompromised and immunocompetent patients. In recent years, new therapeutic approaches have emerged, including immunotherapy and EGFR inhibitors, which have shown efficacy in treating advanced cSCC. Understanding the underlying mechanisms driving cSCC is crucial for developing novel and more effective therapies. This review aims to provide a comprehensive overview of the mutational landscape and microenvironmental factors in cSCC. Cutaneous squamous cell carcinoma (cSCC) manifests through the complex interactions of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. A high mutational burden is present in cSCC, as well as both cSCC precursors and normal skin, making driver genes difficult to differentiate. Despite this, several key driver genes have been identified, including TP53, the NOTCH family, CDKN2A, PIK3CA, and EGFR. In addition to mutations, the tumor microenvironment and the manipulation and evasion of the immune system play a critical role in cSCC progression. Novel therapeutic approaches, such as immunotherapy and EGFR inhibitors, have been used to target these dysregulations, and have shown promise in treating advanced cSCC cases, emphasizing the need for targeted interventions considering both genetic and microenvironmental factors for improved patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Resistance to standard therapies represents a major challenge in melanoma treatment. This is mainly related to the high heterogeneity of this malignancy due to the presence of different types of cells in the tumor mass. Cancer stem cells (CSCs) are a small subset of cells endowed with self-renewal and tumorigenic capacity and the ability to escape anticancer therapies. Melanoma CSCs can be identified by the expression of biomarkers and intracellular pathways deeply involved in their malignant phenotype. Dissecting the molecular mechanisms underlying CSC biological functions might pave the way for novel therapeutic approaches. Herein, we highlight the intricate bidirectional communication between melanoma CSCs and their surrounding cells in the tumor microenvironment and discuss how this interplay might impact the processes of drug resistance and tumor relapse. We also address the potential benefits of CSC-targeted strategies, in combination with conventional drugs, for improving melanoma treatment strategies. Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are a small subpopulation of cells in different tumors, including melanoma, endowed with distinctive capacities of self-renewal and differentiation into bulk tumor cells. Melanoma CSCs are characterized by the expression of specific biomarkers and intracellular pathways; moreover, they play a pivotal role in tumor onset, progression and drug resistance. In recent years, great efforts have been made to dissect the molecular mechanisms underlying the protumor activities of melanoma CSCs to provide the basis for novel CSC-targeted therapies. Herein, we highlight the intricate crosstalk between melanoma CSCs and bystander cells in the tumor microenvironment (TME), including immune cells, endothelial cells and cancer-associated fibroblasts (CAFs), and its role in melanoma progression. Specifically, we discuss the peculiar capacities of melanoma CSCs to escape the host immune surveillance, to recruit immunosuppressive cells and to educate immune cells toward an immunosuppressive and protumor phenotype. We also address currently investigated CSC-targeted strategies that could pave the way for new promising therapeutic approaches for melanoma care. [ABSTRACT FROM AUTHOR]

Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies. [ABSTRACT FROM AUTHOR]

Dysregulation of epidermal growth factor receptor (EGFR) is one of the most common mechanisms associated with the pathogenesis of various cancers. Mitogen‐inducible gene 6 [MIG6; also known as ERBB receptor feedback inhibitor 1 (ERRFI1)], identified as a feedback inhibitor of EGFR, negatively regulates EGFR by directly inhibiting its kinase activity and facilitating its internalization, subsequently leading to degradation. Despite its proposed role as an EGFR‐dependent tumor suppressor, the functional consequences and clinical relevance in cancer etiology remain incompletely understood. Here, we identify that the stoichiometric balance between MIG6 and EGFR is crucial in promoting EGFR‐dependent oncogenic growth in various experimental model systems. In addition, a subset of ERRFI1 (the official gene symbol of MIG6) mutations exhibit impaired ability to suppress the enzymatic activation of EGFR at multiple levels. In summary, our data suggest that decreased or loss of MIG6 activity can lead to abnormal activation of EGFR, potentially contributing to cellular transformation. We propose that the mutation status of ERRFI1 and the expression levels of MIG6 can serve as additional biomarkers for guiding EGFR‐targeted cancer therapies, including glioblastoma. [ABSTRACT FROM AUTHOR]

The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs. The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC). Despite recent advances, it remains challenging to establish causal relationships between microbes and CRC carcinogenesis. In this perspective, we discuss current challenges, recent developments, and research needs. [ABSTRACT FROM AUTHOR]