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KRAS inhibitors: resistance drivers and combinatorial strategies. KRAS抑制剂：耐药驱动和组合策略。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-27 DOI: 10.1016/j.trecan.2024.11.009
Tamara Isermann, Christine Sers, Channing J Der, Bjoern Papke
{"title":"KRAS inhibitors: resistance drivers and combinatorial strategies.","authors":"Tamara Isermann, Christine Sers, Channing J Der, Bjoern Papke","doi":"10.1016/j.trecan.2024.11.009","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.009","url":null,"abstract":"<p><p>In 1982, the RAS genes HRAS and KRAS were discovered as the first human cancer genes, with KRAS later identified as one of the most frequently mutated oncogenes. Yet, it took nearly 40 years to develop clinically effective inhibitors for RAS-mutant cancers. The discovery in 2013 by Shokat and colleagues of a druggable pocket in KRAS paved the way to FDA approval of the first covalently binding KRAS<sup>G12C</sup> inhibitors, sotorasib and adagrasib, in 2021 and 2022, respectively. However, rather than marking the end of a successful assault on the Mount Everest of cancer research, this landmark only revealed new challenges in RAS drug discovery. In this review, we highlight the progress on defining resistance mechanisms and developing combination treatment strategies to improve patient responses to KRAS therapies.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Turning cold into hot: emerging strategies to fire up the tumor microenvironment. 化冷为热：激发肿瘤微环境的新策略。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-26 DOI: 10.1016/j.trecan.2024.11.011
Kaili Ma, Lin Wang, Wenhui Li, Tingting Tang, Bo Ma, Liyuan Zhang, Lianjun Zhang
{"title":"Turning cold into hot: emerging strategies to fire up the tumor microenvironment.","authors":"Kaili Ma, Lin Wang, Wenhui Li, Tingting Tang, Bo Ma, Liyuan Zhang, Lianjun Zhang","doi":"10.1016/j.trecan.2024.11.011","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.011","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm. In this review, we summarize the intrinsic, extrinsic, and systemic factors contributing to the formation of 'cold' tumors within the framework of the cancer-immunity cycle. Correspondingly, we discuss potential strategies for converting 'cold' tumors into 'hot' ones to enhance therapeutic efficacy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cancer immunotherapeutic challenges from autophagy-immune checkpoint reciprocal regulation. 来自自噬-免疫检查点相互调节的癌症免疫治疗挑战。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-19 DOI: 10.1016/j.trecan.2024.11.001
Gang Zhang, Yinfeng Chen, Xing Huang, Tingbo Liang
{"title":"Cancer immunotherapeutic challenges from autophagy-immune checkpoint reciprocal regulation.","authors":"Gang Zhang, Yinfeng Chen, Xing Huang, Tingbo Liang","doi":"10.1016/j.trecan.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.001","url":null,"abstract":"<p><p>Multiple strategies have been clinically employed as combination partners to enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Although these combinations have demonstrated improved effectiveness in some instances, each presents its own limitations. Autophagy-targeting therapy offers several advantages when combined with ICIs, including enhanced tumor immunogenicity, reduced side effects, and broader applicability to diverse patient populations. However, emerging evidence reveals complex reciprocal regulation between autophagy and immune checkpoints which may complicate combination treatments targeting these two systems. This review focuses on the reciprocal interplay between autophagy and immune checkpoints, and provides valuable guidelines for the determination and adjustment of therapeutic regimens in the future.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A hormetic response model for glutamine stress in cancer. 谷氨酰胺应激在癌症中的致敏反应模型。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-16 DOI: 10.1016/j.trecan.2024.11.008
Shea F Grenier, Cosimo Commisso
{"title":"A hormetic response model for glutamine stress in cancer.","authors":"Shea F Grenier, Cosimo Commisso","doi":"10.1016/j.trecan.2024.11.008","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.008","url":null,"abstract":"<p><p>Glutamine metabolism supports the development and progression of many cancers and is considered a therapeutic target. Attempts to inhibit glutamine metabolism have resulted in limited success and have not translated into clinical benefit. The outcomes of these clinical studies, along with preclinical investigations, suggest that cellular stress responses to glutamine deprivation or targeting may be modeled as a biphasic hormetic response. By recognizing the multifaceted aspects of glutamine metabolism inhibition within a more comprehensive biological framework, the adoption of this model may guide future fundamental and translational studies. To achieve clinical efficacy, we posit that as a field we will need to anticipate the hormetic effects of glutamine stress and consider how best to co-target cancer cell adaptive mechanisms.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional heterogeneity of fibroblasts in primary tumors and metastases. 原发性肿瘤和转移瘤中成纤维细胞的功能异质性。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-13 DOI: 10.1016/j.trecan.2024.11.005
Priscilla S W Cheng, Marta Zaccaria, Giulia Biffi
{"title":"Functional heterogeneity of fibroblasts in primary tumors and metastases.","authors":"Priscilla S W Cheng, Marta Zaccaria, Giulia Biffi","doi":"10.1016/j.trecan.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.005","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are abundant components of the tumor microenvironment (TME) of most solid malignancies and have emerged as key regulators of cancer progression and therapy response. Although recent technological advances have uncovered substantial CAF molecular heterogeneity at the single-cell level, defining functional roles for most described CAF populations remains challenging. With the aim of bridging CAF molecular and functional heterogeneity, this review focuses on recently identified functional interactions of CAF subtypes with malignant cells, immune cells, and other stromal cells in primary tumors and metastases. Dissecting the heterogeneous functional crosstalk of specific CAF populations with other components is starting to uncover candidate combinatorial strategies for therapeutically targeting the TME and cancer progression.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intratumoral immune cell manipulations as a strategy to enhance cancer vaccine efficiency. 肿瘤内免疫细胞操作作为一种提高癌症疫苗效率的策略。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-12 DOI: 10.1016/j.trecan.2024.11.007
James Adeosun, Mohammad Omar Faruk Shaikh, Timothy Brauns, Yuki Agarwala, Mark C Poznansky, Yohannes Gemechu
{"title":"Intratumoral immune cell manipulations as a strategy to enhance cancer vaccine efficiency.","authors":"James Adeosun, Mohammad Omar Faruk Shaikh, Timothy Brauns, Yuki Agarwala, Mark C Poznansky, Yohannes Gemechu","doi":"10.1016/j.trecan.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.007","url":null,"abstract":"<p><p>Shortcomings in cancer vaccine development are attributable to weak and transient anti-tumor cellular responses in the tumor microenvironment. This restriction of efficacy may be due to an intratumoral immunosuppressive milieu, consisting of regulatory T cells, M2 macrophages, and myeloid derived suppressor cells. Here, we analyze recent advances and propose future directions in the modulation of cellular state propensities combined with cancer vaccines.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Short-chain fatty acids and cancer. 短链脂肪酸和癌症。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-04 DOI: 10.1016/j.trecan.2024.11.003
Shan Li, Yixin Duan, Shudi Luo, Fangxin Zhou, Qingang Wu, Zhimin Lu
{"title":"Short-chain fatty acids and cancer.","authors":"Shan Li, Yixin Duan, Shudi Luo, Fangxin Zhou, Qingang Wu, Zhimin Lu","doi":"10.1016/j.trecan.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.003","url":null,"abstract":"<p><p>Short-chain fatty acids (SCFAs), derived from the diet and the microbiota, serve as crucial links between the diet, gut microbiota, metabolism, immunity, and cancer. They function as energy sources through β-oxidation and regulate macromolecular synthesis, G protein-coupled receptor (GPCR) and histone deacetylase (HDAC) activities, protein modifications, signaling pathways, and gene expression in cells within the tumor microenvironment, particularly in tumor and immune cells. The critical role of SCFAs in maintaining normal homeostasis and influencing tumor progression highlights the potential of targeting SCFA-mediated cellular processes for cancer prevention and treatment.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic immune escape in cancer: timing and implications for treatment. 癌症的遗传免疫逃逸：治疗的时机和意义。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-03 DOI: 10.1016/j.trecan.2024.11.002
Francisco Martínez-Jiménez, Diego Chowell
{"title":"Genetic immune escape in cancer: timing and implications for treatment.","authors":"Francisco Martínez-Jiménez, Diego Chowell","doi":"10.1016/j.trecan.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.002","url":null,"abstract":"<p><p>Genetic immune escape (GIE) alterations pose a significant challenge in cancer by enabling tumors to evade immune detection. These alterations, which can vary significantly across cancer types, may often arise early in clonal evolution and contribute to malignant transformation. As tumors evolve, GIE alterations are positively selected, allowing immune-resistant clones to proliferate. In addition to genetic changes, the tumor microenvironment (TME) and non-genetic factors such as inflammation, smoking, and environmental exposures play crucial roles in promoting immune evasion. Understanding the timing and mechanisms of GIE, alongside microenvironmental influences, is crucial for improving early detection and developing more effective therapeutic interventions. This review highlights the implications of GIE in cancer development and immunotherapy resistance, and emphasizes the need for integrative approaches.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neoadjuvant combination immunotherapy in MSI/dMMR colorectal cancer. MSI/dMMR 大肠癌的新辅助联合免疫疗法。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-01 Epub Date: 2024-10-24 DOI: 10.1016/j.trecan.2024.10.006
Meggy Suarez-Carmona, Niels Halama
{"title":"Neoadjuvant combination immunotherapy in MSI/dMMR colorectal cancer.","authors":"Meggy Suarez-Carmona, Niels Halama","doi":"10.1016/j.trecan.2024.10.006","DOIUrl":"10.1016/j.trecan.2024.10.006","url":null,"abstract":"<p><p>Neoadjuvant immune checkpoint inhibition (ICI) is a new approach to treat patients with colorectal cancer (CRC). The effects of combined neoadjuvant ICI in locally advanced, DNA mismatch repair (dMMR)-deficient/microsatellite instable (MSI) CRC were recently reported by de Gooyer et al. from the NICHE-3 trial. Further studies will determine whether these impressive pathological responses lead to long-term clinical benefit.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1093-1094"},"PeriodicalIF":14.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
EZHIP's role in diffuse midline glioma: echoes of oncohistones? EZHIP 在弥漫性中线胶质瘤中的作用：与癌基因的呼应？
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-01 Epub Date: 2024-09-28 DOI: 10.1016/j.trecan.2024.09.002
Afraah Cassim, Matthew D Dun, David Gallego-Ortega, Fatima Valdes-Mora
{"title":"EZHIP's role in diffuse midline glioma: echoes of oncohistones?","authors":"Afraah Cassim, Matthew D Dun, David Gallego-Ortega, Fatima Valdes-Mora","doi":"10.1016/j.trecan.2024.09.002","DOIUrl":"10.1016/j.trecan.2024.09.002","url":null,"abstract":"<p><p>The enhancer of zeste inhibitory protein (EZHIP) is typically expressed during germ cell development and has been classified as a cancer-testis antigen (CTA) in various cancers. In 2020, 4% of diffuse midline gliomas (DMGs) were shown to aberrantly express EZHIP, mirroring the DMG hallmark histone H3 K27M (H3K27M) oncohistone mutation. Similar to H3K27M, EZHIP is a negative regulator of polycomb repressive complex 2 (PRC2), leading to global epigenomic remodeling. In this opinion, we explore the similarities and disparities between H3K27M- and EZHIP-DMGs with a focus on their shared functional hallmark of PRC2 inhibition, their genetic and epigenomic landscapes, plausible differences in the cell of origin, and therapeutic avenues. Upcoming research on EZHIP will help better understand its role in gliomagenesis and DMG therapy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1095-1105"},"PeriodicalIF":14.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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