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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 : 2025-02-01 Epub 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":"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":"117-134"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","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
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 : 2025-02-01 Epub 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":"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":"135-153"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","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
Transcriptional regulation of hypoxic cancer cell metabolism and artificial intelligence. 缺氧癌细胞新陈代谢的转录调控与人工智能。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-02-01 Epub Date: 2024-10-30 DOI: 10.1016/j.trecan.2024.10.003
Luana Schito, Sergio Rey-Keim
{"title":"Transcriptional regulation of hypoxic cancer cell metabolism and artificial intelligence.","authors":"Luana Schito, Sergio Rey-Keim","doi":"10.1016/j.trecan.2024.10.003","DOIUrl":"10.1016/j.trecan.2024.10.003","url":null,"abstract":"<p><p>Gene expression regulation in hypoxic tumor microenvironments is mediated by O<sub>2</sub> responsive transcription factors (O<sub>2</sub>R-TFs), fine-tuning cancer cell metabolic demand for O<sub>2</sub> according to its availability. Here, we discuss key O<sub>2</sub>R-TFs and emerging artificial intelligence (AI)-based applications suitable for the interrogation of O<sub>2</sub>R-TF relationships specifying cancer cell metabolic adaptations to hypoxia.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"88-90"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558877","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 new enhancer for anti-PD-1/PD-L1 immunotherapy: PCSK9 inhibition. 抗 PD-1/PD-L1 免疫疗法的新增强剂：PCSK9 抑制剂
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-02-01 Epub Date: 2024-10-24 DOI: 10.1016/j.trecan.2024.10.002
Shengbo Sun, Zhengyang Yang, Hongwei Yao, Zhongtao Zhang
{"title":"A new enhancer for anti-PD-1/PD-L1 immunotherapy: PCSK9 inhibition.","authors":"Shengbo Sun, Zhengyang Yang, Hongwei Yao, Zhongtao Zhang","doi":"10.1016/j.trecan.2024.10.002","DOIUrl":"10.1016/j.trecan.2024.10.002","url":null,"abstract":"<p><p>Anti-programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) immunotherapy has shown promising results in cancer treatment, improving clinical outcomes and prolonging patient survival. However, most patients exhibit low response rates to PD-1/PD-L1 blockade, highlighting the urgent need for new enhancers. Increasing data now demonstrate that inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine proteinase, can enhance the antitumor efficacy of anti-PD-1/PD-L1 immunotherapy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"84-87"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508856","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 : 2025-02-01 Epub 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":"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":"91-116"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","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
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 : 2025-02-01 Epub 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":"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":"154-168"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","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
Revumenib: a new era in acute leukemia treatment. Revumenib：急性白血病治疗的新时代。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-02-01 Epub Date: 2025-01-24 DOI: 10.1016/j.trecan.2025.01.006
David A Martínez-Gamboa, Justin Kaner
{"title":"Revumenib: a new era in acute leukemia treatment.","authors":"David A Martínez-Gamboa, Justin Kaner","doi":"10.1016/j.trecan.2025.01.006","DOIUrl":"10.1016/j.trecan.2025.01.006","url":null,"abstract":"<p><p>The AUGMENT-101 clinical trial reported that the use of revumenib led to improved overall survival (OS) and complete remission (CR)/CR with partial hematologic recovery (CRh) in patients with acute leukemias and has released updated data with longer follow-up of Phase 2 results. Additionally, revumenib has received FDA approval for its use in relapsed or refractory (r/r) lysine methyltransferase 2A rearranged (KMT2A-r) acute leukemias.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"81-83"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042373","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
Think zebras: challenges and opportunities for treating rare cancers. 想想斑马：治疗罕见癌症的挑战和机遇。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-02-01 Epub Date: 2025-01-28 DOI: 10.1016/j.trecan.2025.01.004
Sam Behjati, Jesse S Boehm, Matthew D Dun, Stefan Fröhling, Paul H Huang, Nada Jabado, Ning Li, Carla Daniela Robles-Espinoza
{"title":"Think zebras: challenges and opportunities for treating rare cancers.","authors":"Sam Behjati, Jesse S Boehm, Matthew D Dun, Stefan Fröhling, Paul H Huang, Nada Jabado, Ning Li, Carla Daniela Robles-Espinoza","doi":"10.1016/j.trecan.2025.01.004","DOIUrl":"10.1016/j.trecan.2025.01.004","url":null,"abstract":"","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"75-80"},"PeriodicalIF":14.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060832","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
Mitochondrial DNA damage, repair, and replacement in cancer. 癌症中的线粒体 DNA 损伤、修复和替代。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-01-01 Epub Date: 2024-10-21 DOI: 10.1016/j.trecan.2024.09.010
Pavel Vodicka, Sona Vodenkova, Natalie Danesova, Ludmila Vodickova, Renata Zobalova, Kristyna Tomasova, Stepana Boukalova, Michael V Berridge, Jiri Neuzil
{"title":"Mitochondrial DNA damage, repair, and replacement in cancer.","authors":"Pavel Vodicka, Sona Vodenkova, Natalie Danesova, Ludmila Vodickova, Renata Zobalova, Kristyna Tomasova, Stepana Boukalova, Michael V Berridge, Jiri Neuzil","doi":"10.1016/j.trecan.2024.09.010","DOIUrl":"10.1016/j.trecan.2024.09.010","url":null,"abstract":"<p><p>Mitochondria are vital organelles with their own DNA (mtDNA). mtDNA is circular and composed of heavy and light chains that are structurally more accessible than nuclear DNA (nDNA). While nDNA is typically diploid, the number of mtDNA copies per cell is higher and varies considerably during development and between tissues. Compared with nDNA, mtDNA is more prone to damage that is positively linked to many diseases, including cancer. Similar to nDNA, mtDNA undergoes repair processes, although these mechanisms are less well understood. In this review, we discuss the various forms of mtDNA damage and repair and their association with cancer initiation and progression. We also propose horizontal mitochondrial transfer as a novel mechanism for replacing damaged mtDNA.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"62-73"},"PeriodicalIF":14.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508857","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
Advances in LAG3 cancer immunotherapeutics. LAG3 癌症免疫疗法的进展。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-01-01 Epub Date: 2024-11-26 DOI: 10.1016/j.trecan.2024.10.009
Kieran Adam, Samuel C Butler, Creg J Workman, Dario A A Vignali
{"title":"Advances in LAG3 cancer immunotherapeutics.","authors":"Kieran Adam, Samuel C Butler, Creg J Workman, Dario A A Vignali","doi":"10.1016/j.trecan.2024.10.009","DOIUrl":"10.1016/j.trecan.2024.10.009","url":null,"abstract":"<p><p>Cancer treatment has entered the age of immunotherapy. Immune checkpoint inhibitor (ICI) therapy has shown robust therapeutic potential in clinical practice, with significant improvements in progression-free survival (PFS) and overall survival (OS). Recently, checkpoint blockade of the lymphocyte activation gene 3 (LAG3) inhibitory receptor (IR) in combination with programmed death protein 1 (PD1) inhibition has been FDA approved in patients with advanced melanoma. This has encouraged the clinical evaluation of new LAG3-directed biologics in combination with other checkpoint inhibitors. Several of these studies are evaluating bispecific antibodies that target exhausted T (T<sub>EX</sub>) cells expressing multiple IRs. This review discusses the current understanding of LAG3 in regulating antitumor immunity and the ongoing clinical testing of LAG3 inhibition in cancer.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"37-48"},"PeriodicalIF":14.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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