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Generation of tumor neoantigens by RNA splicing perturbation. 通过 RNA 剪接扰乱生成肿瘤新抗原。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-01-01 Epub Date: 2024-11-22 DOI: 10.1016/j.trecan.2024.10.008
Adi Rosenberg-Mogilevsky, Zahava Siegfried, Rotem Karni
{"title":"Generation of tumor neoantigens by RNA splicing perturbation.","authors":"Adi Rosenberg-Mogilevsky, Zahava Siegfried, Rotem Karni","doi":"10.1016/j.trecan.2024.10.008","DOIUrl":"10.1016/j.trecan.2024.10.008","url":null,"abstract":"<p><p>Immunotherapy has revolutionized cancer treatment, but the limited availability of tumor-specific neoantigens still remains a challenge. The potential of alternative mRNA splicing-derived neoantigens as a source of new immunotherapy targets has gained significant attention. Tumors exhibit unique splicing changes and splicing factor mutations which are prevalent in various cancers and play a crucial role in neoantigen production. We present advances in splicing modulation approaches, including small-molecule drugs, decoy and splice-switching antisense oligonucleotides (SSOs), CRISPR, small interfering RNAs (siRNAs), and nonsense-mediated RNA decay (NMD) inhibition, that can be adapted to enhance antitumor immune responses. Finally, we explore the clinical implications of these approaches, highlighting their potential to transform cancer immunotherapy and broaden its efficacy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"12-24"},"PeriodicalIF":14.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693709","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
Exercise against nonsmall-cell lung carcinoma: novel insights. 运动对抗非小细胞肺癌：新见解。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-01-01 Epub Date: 2024-12-04 DOI: 10.1016/j.trecan.2024.11.006
Abel Plaza-Florido, Carmen Fiuza-Luces, Alejandro Lucia
{"title":"Exercise against nonsmall-cell lung carcinoma: novel insights.","authors":"Abel Plaza-Florido, Carmen Fiuza-Luces, Alejandro Lucia","doi":"10.1016/j.trecan.2024.11.006","DOIUrl":"10.1016/j.trecan.2024.11.006","url":null,"abstract":"<p><p>The mechanisms underlying the potential 'anticancer' effects of exercise remain poorly understood. Luo et al. recently identified an exercise-induced, muscle-derived extracellular vesicle (EV)-associated miR, miR-29a-3p, as a key player in the potential benefits of exercise against nonsmall-cell lung carcinoma (NSCLC), including extracellular matrix (ECM) inhibition and improved antitumoral immune responses.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1-3"},"PeriodicalIF":14.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787132","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
Regulation of metastatic organotropism. 转移性器官性的调节。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-27 DOI: 10.1016/j.trecan.2024.11.012
Karen J Dunbar, Gizem Efe, Katherine Cunningham, Emily Esquea, Raul Navaridas, Anil K Rustgi
{"title":"Regulation of metastatic organotropism.","authors":"Karen J Dunbar, Gizem Efe, Katherine Cunningham, Emily Esquea, Raul Navaridas, Anil K Rustgi","doi":"10.1016/j.trecan.2024.11.012","DOIUrl":"10.1016/j.trecan.2024.11.012","url":null,"abstract":"<p><p>Metastasis is responsible for most cancer-related deaths. Different cancers have their own preferential sites of metastases, a phenomenon termed metastatic organotropism. The mechanisms underlying organotropism are multifactorial and include the generation of a pre-metastatic niche (PMN), metastatic homing, colonization, dormancy, and metastatic outgrowth. Historically, studies of metastatic organotropism have been limited by a lack of models allowing direct comparison of cells exhibiting different patterns of tropism. However, new innovative models and large-scale sequencing efforts have propelled organotropism research. Herein, we summarize the recent discoveries in metastatic organotropism regulation, focusing on lung, liver, brain, and bone tropism. We discuss how emerging technologies are continuing to improve our ability to model and, hopefully, predict and treat organotropism.</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":"142898412","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
Cellular senescence offers distinct immunological vulnerabilities in cancer. 细胞衰老在癌症中提供了独特的免疫脆弱性。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-27 DOI: 10.1016/j.trecan.2024.11.010
Lin Zhou, Boyang Ma, Marcus Ruscetti
{"title":"Cellular senescence offers distinct immunological vulnerabilities in cancer.","authors":"Lin Zhou, Boyang Ma, Marcus Ruscetti","doi":"10.1016/j.trecan.2024.11.010","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.11.010","url":null,"abstract":"<p><p>Chronic damage following oncogene induction or cancer therapy can produce cellular senescence. Senescent cells not only exit the cell cycle but communicate damage signals to their environment that can trigger immune responses. Recent work has revealed that senescent tumor cells are highly immunogenic, leading to new ways to activate antitumor immunosurveillance and potentiate T cell-directed immunotherapies. However, other studies have determined that heterogeneous senescent stromal cell populations contribute to immunosuppression and tumor progression, sparking the development of senotherapeutics to target senescent cells that evade immune detection. We review current findings that provide deeper insights into the mechanisms contributing to the dichotomous role of senescence in immune modulation and how that can be leveraged for cancer immunotherapy.</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":"142898403","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
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
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