Journal of cancer biology最新文献

{"title":"Beyond a binary RTK-RAS biomarker: context-aware precision oncology in early-onset colorectal cancer.","authors":"Enrique Velazquez-Villarreal","doi":"10.46439/cancerbiology.7.085","DOIUrl":"https://doi.org/10.46439/cancerbiology.7.085","url":null,"abstract":"<p><p>Early-onset colorectal cancer (EOCRC) is increasing worldwide and represents a biologically and clinically heterogeneous disease that requires precision approaches extending beyond conventional single-gene biomarkers. Recent analyses of receptor tyrosine kinase-RAS (RTK-RAS) pathway alterations demonstrate that their clinical significance is strongly dependent on age at diagnosis, ancestry, and treatment exposure. In particular, RTK-RAS alterations have been associated with unfavorable survival in untreated early-onset non-Hispanic White colorectal cancer, while an opposite association has been observed in FOLFOX-treated late-onset disease. At the same time, overall RTK-RAS pathway alteration frequencies remain relatively stable across patient groups, whereas gene-specific differences involving ERBB2, NF1, FGFR2, NTRK2, and other pathway components reveal substantial molecular heterogeneity. These observations challenge the use of RTK-RAS alteration status as a uniform prognostic biomarker and instead support a context-dependent model in which genomic alterations interact with age-related tumor biology, treatment pressures, ancestry-associated factors, and broader molecular states. Emerging genomic studies further suggest that EOCRC may harbor distinct mutational processes related to earlier-life exposures, reinforcing the need to integrate pathway alterations with mutational signatures, tumor microenvironment features, and multi-omic information. Artificial intelligence-enabled platforms such as AI-HOPE, developed at the Velazquez-Villarreal Lab at City of Hope, provide a scalable strategy for interrogating these complex multidimensional relationships through rapid cohort construction and hypothesis generation, while maintaining conventional statistical and experimental validation as essential components of inference. Future studies incorporating diverse populations, detailed treatment histories, genomic ancestry, longitudinal sampling, and functional validation will be critical for determining whether context-specific RTK-RAS patterns can ultimately improve risk stratification and therapeutic selection in EOCRC.</p>","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"7 1","pages":"19-25"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the understanding of health disparities in the United States Hispanic population.","authors":"Asma Pinkey, Masuma Anzuman, Mrudang Desai, Anna M Eiring","doi":"10.46439/cancerbiology.6.076","DOIUrl":"10.46439/cancerbiology.6.076","url":null,"abstract":"<p><p>Health disparities have become a major concern for global public health, disproportionately affecting minority and underserved populations throughout the United States (U.S.). Hispanics make up the fastest-growing minority group in the U.S., and they often experience significant health disparities when it comes to chronic diseases such as cancer, cardiovascular disease, and diabetes. These disparities are likely driven by a confluence of socioeconomic disadvantages, structural inequities, environmental exposures, and cultural barriers. While Hispanics experience a disproportionate burden of incidence and mortality, they may paradoxically exhibit improved survival compared to non-Hispanic Whites, as is the case for hepatocellular carcinoma. This phenomenon is termed the Hispanic paradox. This review summarizes current evidence on well-known factors such as age, sex and gender, socioeconomic status, neighborhood poverty, insurance type, and diet, as well as less-known factors, including environmental exposures, lifestyle, and cultural differences that influence health outcomes in Hispanics. It also highlights critical gaps in disaggregated data that limit a complete understanding of these disparities until further subgroup-specific analyses are performed. Ultimately, the commentary calls for culturally competent care, inclusive research that accounts for heterogeneity within Hispanic groups, and public health policies that not only reduce structural inequities but also comprehensively improve healthcare access, affordability, and lifestyle support.</p>","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"6 1","pages":"71-75"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12795592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.","authors":"Kailey P Caroland, Jonathan B Trapani, Ethan Lee, Vivian L Weiss","doi":"10.46439/cancerbiology.6.079","DOIUrl":"10.46439/cancerbiology.6.079","url":null,"abstract":"<p><p>Wnt signaling has long been implicated in cancer development, but recent studies have revealed new insights into how Wnt ligands themselves drive metastasis. Currently, research identifies Wnt1, Wnt2, Wnt2b, Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt6, Wnt8a, Wnt9b, Wnt10a, Wnt10b, and Wnt16 as pro-metastatic Wnt ligands, while Wnt7a, Wnt7b, Wnt8b, Wnt9a, and Wnt11 exhibit conflicting pro- and anti-metastatic roles. These ligands arise from diverse sources in the tumor microenvironment and perform a wide range of roles in the metastatic cascade, including epithelial-to-mesenchymal transition, matrix metalloproteinase production, cell motility, angiogenesis, cell death resistance, and mesenchymal-to-epithelial transition. Their diverse and critical roles in metastasis make Wnt ligands attractive therapeutic targets.</p>","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"6 2","pages":"91-107"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton Sensing GPCR's: The missing link to Warburg's Oncogenic Legacy?","authors":"Jessica Cornell, Samantha Rea, Leif R Neitzel, Charles H Williams, Charles C Hong","doi":"10.46439/cancerbiology.5.066","DOIUrl":"10.46439/cancerbiology.5.066","url":null,"abstract":"<p><p>A century after Otto Warburg's seminal discovery of aerobic glycolysis in cancer cells, a phenomenon dubbed the \"Warburg effect\", the mechanistic links between this metabolic rewiring and tumorigenesis remain elusive. Warburg postulated that this enhanced glucose fermentation to lactate, even in the presence of oxygen, stemmed from an \"irreversible respiratory injury\" intrinsic to cancer cells. While oxidative phosphorylation yields higher ATP, the Warburg effect paradoxically persists, suggesting that the excess lactate and acid production are worth the deficit. Since Warburg's discovery, it has been demonstrated that the acidic tumor microenvironment activates a myriad of pro-oncogenic phenotypes ranging from therapeutic resistance to immune escape. Here we propose that proton-sensing G-protein-coupled receptors (GPCRs) act as crucial heirs to Warburg's findings by transducing the acid signal from elevated glycolytic lactate into pro-oncogenic signals. The increased lactate production characteristic of the Warburg effect causes extracellular acidification. This acidic tumor microenvironment can activate proton-sensing GPCRs like GPR68, a proton-sensing receptor shown to stimulate proliferation, migration, and survival pathways in cancer cells. Such pH sensing is accomplished through protonation of key residues such as histidine, which causes a conformational change to activate various downstream signaling cascades including the MAPK, PI3K/Akt, Rho, and β-arrestin pathways implicated in tumor progression and therapeutic resistance. By coupling Warburg's \"respiratory injury\" to potent mitogenic signaling, proton-sensing GPCRs like GPR68 may unveil a longstanding mystery - why forgo efficient ATP generation? As heirs to Warburg's iconic metabolic observations, these proton sensors could represent novel therapeutic targets to disrupt the synergy between the Warburg effect and oncogenic signaling.</p>","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"5 2","pages":"65-75"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The many faceted role of glycogen synthase kinase-3 (GSK-3) in T cells and cancer immunotherapy.","authors":"Aurora Rivas Crespo, Silvia Guil Luna, Bastien Moës, Antonio Rodriguez, Christopher E Rudd","doi":"10.46439/cancerbiology.5.058","DOIUrl":"10.46439/cancerbiology.5.058","url":null,"abstract":"","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"5 1","pages":"11-16"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141177046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the PRMT1-cGAS-STING signaling pathway to enhance the anti-tumor therapeutic efficacy.","authors":"Daoyuan Huang, Abdol-Hossein Rezaeian, Jingchao Wang, Yihang Qi, Hong Chen, Hiroyuki Inuzuka, Wenyi Wei","doi":"10.46439/cancerbiology.5.064","DOIUrl":"10.46439/cancerbiology.5.064","url":null,"abstract":"<p><p>Activating innate immune signaling in tumor cells to enhance anti-tumor immunity and increase T cell-mediated killing is the core objective of tumor immunotherapy. PRMT1, one of the most crucial PRMTs, plays a critical role in tumor progression and innate immunity. Recent research revealed that PRMT1 can inhibit the enzymatic activity of cGAS in part through PRMT1-mediated Arg methylation, thereby suppressing the anti-tumor immune response of cells. As such, inhibiting or knocking down PRMT1 can synergistically enhance the efficacy of anti-PD-1 immunotherapy by activating the cGAS-STING signaling pathway. Here, we provide a comprehensive description of the two key signaling components, PRMT1 and cGAS, in the PRMT1-cGAS-STING signaling pathway for therapeutic intervention to augment anti-tumor immunity. By understanding the specific physiological functions and regulatory mechanisms of PRMT1, as well as the extensive post-translational modifications (PTMs) of cGAS, we have identified several compounds and drugs that can directly target PRMT1 or cGAS, and/or indirectly target PRMT1 upstream regulators or cGAS-post-translational modifying enzymes as potential means to activate the cGAS-STING signaling pathway. However, further investigation is needed on the efficacy of combining this pathway activation with anti-PD1 therapy. This review suggests that targeting the PRMT1-cGAS-STING pathway with immune checkpoint inhibitors is likely a promising approach in tumor immunotherapy.</p>","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"5 2","pages":"44-60"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}