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Advances in menin inhibition in acute myeloid leukemia. 急性髓系白血病中menin抑制的研究进展。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-03 DOI: 10.1016/j.trecan.2025.06.002
Leora Boussi, Sheng F Cai, Eytan M Stein
{"title":"Advances in menin inhibition in acute myeloid leukemia.","authors":"Leora Boussi, Sheng F Cai, Eytan M Stein","doi":"10.1016/j.trecan.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.trecan.2025.06.002","url":null,"abstract":"<p><p>Menin has emerged as a promising therapeutic target in acute myeloid leukemia (AML). The menin-MLL1 interaction promotes an oncogenic transcriptional program that drives leukemogenesis in HOX-mediated acute leukemias, including KMT2A-rearranged (KMT2Ar), nucleophosmin 1-mutated (NPM1m), and NUP98-rearranged (NUP98r) AML, prompting development of menin inhibitors for treatment of these subtypes. Successes in clinical investigation have led to recent FDA approval of revumenib for KMT2Ar AML, with numerous trials examining menin inhibitors as monotherapy and in combination with other antileukemic drugs ongoing. Although menin inhibitors represent a major advancement in AML treatment, acquired resistance is an evolving barrier to efficacy. Here, we examine the biological rationale for menin inhibition and discuss the landscape of clinical trials and resistance mechanisms associated with menin inhibitors.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565271","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
Beyond safety: suicide systems in cell-based cancer therapies. 超越安全：细胞癌症治疗中的自杀系统。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-03 DOI: 10.1016/j.trecan.2025.06.003
Kok-Siong Chen, Khalid Shah
{"title":"Beyond safety: suicide systems in cell-based cancer therapies.","authors":"Kok-Siong Chen, Khalid Shah","doi":"10.1016/j.trecan.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.trecan.2025.06.003","url":null,"abstract":"<p><p>Cell-based therapies are promising for treating solid tumors, but challenges like tumor heterogeneity, antigen escape, and immunosuppressive microenvironments hinder their efficacy. Inducible suicide gene systems, often viewed solely as safety mechanisms, offer an underappreciated opportunity to enhance cellular therapies. These systems, triggered by various mechanisms (prodrugs, ligands, antibodies, or small molecules), enable controlled elimination of therapeutic cells. Recent developments demonstrate that this controlled cell death, especially when inducing immunogenic cell death (ICD), can kill even resistant tumor cells and reshape the tumor microenvironment (TME) from suppressive to stimulatory. This review highlights the transformative potential of integrating these suicide systems into cell therapies, overcoming key limitations, and amplifying antitumor responses while ensuring safety.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565272","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
mtDNA transfer from senescent cancer cells to MDSCs promotes immunosuppression. mtDNA从衰老癌细胞转移到MDSCs促进免疫抑制。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-02 DOI: 10.1016/j.trecan.2025.06.010
Israel Cañadas, Takahiko Murayama, Lorenzo Galluzzi
{"title":"mtDNA transfer from senescent cancer cells to MDSCs promotes immunosuppression.","authors":"Israel Cañadas, Takahiko Murayama, Lorenzo Galluzzi","doi":"10.1016/j.trecan.2025.06.010","DOIUrl":"https://doi.org/10.1016/j.trecan.2025.06.010","url":null,"abstract":"<p><p>Sublethal apoptotic stress causing the permeabilization of some mitochondria coupled with cytosolic mitochondrial DNA (mtDNA) accumulation is known to promote cellular senescence. Lai et al. have recently demonstrated that this may be accompanied by mtDNA release within extracellular vesicles that promote local immunosuppression via myeloid-derived suppressor cells.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561298","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
The future of tumor organoids in precision therapy. 肿瘤类器官在精准治疗中的未来。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-01 Epub Date: 2025-04-03 DOI: 10.1016/j.trecan.2025.03.005
Seok-Young Kim, Marc van de Wetering, Hans Clevers, Karin Sanders
{"title":"The future of tumor organoids in precision therapy.","authors":"Seok-Young Kim, Marc van de Wetering, Hans Clevers, Karin Sanders","doi":"10.1016/j.trecan.2025.03.005","DOIUrl":"10.1016/j.trecan.2025.03.005","url":null,"abstract":"<p><p>Tumoroids are cultures of patient-derived tumor cells, which are grown in 3D in the presence of an extracellular matrix extract and specific growth factors. Tumoroids can be generated from adult as well as pediatric cancers, including epithelial cancers, sarcomas, and brain cancers. Tumoroids retain multi-omic characteristics of their corresponding tumor and recapitulate interpatient and intratumor heterogeneity. Retrospective and prospective studies have demonstrated that tumoroids predict patient responses to anticancer therapies, making them a promising tool for precision oncology. However, several challenges remain before tumoroids can be fully integrated into clinical decision-making, including success rates of tumoroid establishment and turnaround times. This review discusses the current advances, challenges, and future directions of tumoroid-based models in cancer research and precision therapy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"665-675"},"PeriodicalIF":14.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789244","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
Inciting commensal human papillomavirus immunity to combat cancer. 激发人类乳头瘤病毒共生免疫以对抗癌症。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-01 Epub Date: 2025-05-01 DOI: 10.1016/j.trecan.2025.04.006
Natalie E Fulton, Thomas D Horn, Shadmehr Demehri
{"title":"Inciting commensal human papillomavirus immunity to combat cancer.","authors":"Natalie E Fulton, Thomas D Horn, Shadmehr Demehri","doi":"10.1016/j.trecan.2025.04.006","DOIUrl":"10.1016/j.trecan.2025.04.006","url":null,"abstract":"<p><p>The incidence of squamous cell carcinoma (SCC) is rising, especially in immunosuppressed individuals, highlighting the need for new prevention strategies. Commensal human papillomaviruses (cHPVs) are associated with cutaneous SCC (cSCC) in immunosuppressed patients. Because of the intricate interactions between T cell immunity and cHPVs in virus-colonized tissues, we propose that enhancing T cell immunity against cHPVs through vaccination could suppress SCC.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"616-618"},"PeriodicalIF":14.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064826","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
Repurposing glucose-lowering drugs for cancer therapy. 将降糖药物用于癌症治疗。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-01 Epub Date: 2025-05-15 DOI: 10.1016/j.trecan.2025.04.010
Michaela Luconi, Giulia Cantini, Clara Crescioli
{"title":"Repurposing glucose-lowering drugs for cancer therapy.","authors":"Michaela Luconi, Giulia Cantini, Clara Crescioli","doi":"10.1016/j.trecan.2025.04.010","DOIUrl":"10.1016/j.trecan.2025.04.010","url":null,"abstract":"<p><p>The acknowledged relationship between metabolism and cancer retains important potential as a novel target in therapy. Reallocating glucose-lowering drugs (GLDs) in cancer treatment offers valuable perspectives for the ability of these molecules to regulate metabolism at cellular and systemic level. This comprehensive review addresses the therapeutic potential of the main antidiabetic classes of glucose-lowering drugs with emerging anticancer effects, such as metformin, rosiglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium/glucose cotransporter-2 inhibitors. The multifaceted actions of these drugs are explored, from in vitro evidence to clinical evidence as monotherapy or as a sparing agent with chemotherapy and immunotherapy. For each molecule, unconventional mechanisms, benefits, and limitations are dissected and possible concerns addressed, supporting evidence for the potential use of the drug in cancer.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"691-710"},"PeriodicalIF":14.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080674","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
New insights into tryptophan metabolism in cancer. 癌症中色氨酸代谢的新见解。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-01 Epub Date: 2025-04-23 DOI: 10.1016/j.trecan.2025.03.008
Zhe Qi Liu, M Teresa Ciudad, Tracy L McGaha
{"title":"New insights into tryptophan metabolism in cancer.","authors":"Zhe Qi Liu, M Teresa Ciudad, Tracy L McGaha","doi":"10.1016/j.trecan.2025.03.008","DOIUrl":"10.1016/j.trecan.2025.03.008","url":null,"abstract":"<p><p>Tryptophan (Trp) is an essential amino acid and key intermediate in a range of biological processes. Early studies identified altered Trp utilization in cancer cells favoring cancer survival and growth. Seminal findings linking Trp metabolism and suppression of immunity led to an explosion of interest ultimately culminating in clinical trials targeting these pathways in melanoma. The failure of these trials led to a clinical retreat in this approach; however, recent insights into the complex interplay of the various Trp circuits and between tumor cells, immune cells, and the microbiota have shown that reconsideration of Trp metabolism is needed. Here, we discuss recent developments in our understanding of Trp metabolism and apparent contradictions in the field. We also discuss adaptations that occur when Trp pathways are manipulated, which may impact therapy responses.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"629-641"},"PeriodicalIF":14.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996844","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
Prospects for understanding and exploiting the consequences of hyperactivation lethality. 理解和利用过度激活致死性后果的前景。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-01 Epub Date: 2025-05-19 DOI: 10.1016/j.trecan.2025.04.009
Katharin Shaw, René Bernards, Kimberly Stegmaier, Harold Varmus, William R Sellers
{"title":"Prospects for understanding and exploiting the consequences of hyperactivation lethality.","authors":"Katharin Shaw, René Bernards, Kimberly Stegmaier, Harold Varmus, William R Sellers","doi":"10.1016/j.trecan.2025.04.009","DOIUrl":"10.1016/j.trecan.2025.04.009","url":null,"abstract":"<p><p>Cancer cells optimize oncogenic signaling to maintain a defined range for survival. The success of targeted therapeutic inhibitors is based on suppressing signaling below this optimal fitness zone. Conversely, cancers are also susceptible to a clinically underutilized vulnerability - oncogenic hyperactivation. Cytotoxic hyperactivation is observed across diverse cancers, with direct small-molecule activators and inhibitors of negative regulators inducing lethal pathway activation. Deep characterization of the cancer genome and unbiased screening approaches have yielded multiple targets vulnerable to hyperactivation; however, translation into the clinical setting will require defining signaling thresholds, discovering biomarkers, and developing appropriate trial designs. By exploiting cancer's intrinsic vulnerabilities, activation lethality offers a promising therapeutic strategy to expand the treatment landscape and overcome resistance to targeted inhibition.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"619-628"},"PeriodicalIF":14.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112246","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
Spliced to kill: RNA mis-splicing derived cancer neoantigens. 剪接致死：RNA错误剪接衍生的癌症新抗原。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-01 Epub Date: 2025-06-19 DOI: 10.1016/j.trecan.2025.06.001
Anurag V Prabhu, Carla Azar-Koussa, Zahava Siegfried, Rotem Karni
{"title":"Spliced to kill: RNA mis-splicing derived cancer neoantigens.","authors":"Anurag V Prabhu, Carla Azar-Koussa, Zahava Siegfried, Rotem Karni","doi":"10.1016/j.trecan.2025.06.001","DOIUrl":"10.1016/j.trecan.2025.06.001","url":null,"abstract":"<p><p>One of the major challenges in using neoantigen-based approaches in cancer treatment is the identification of cancer-specific neoantigens, particularly those that are shared by patients. In a recent report, Kim et al. uncover a novel source of cancer neoantigens in splicing factor mutant myeloid malignancies. These mis-spliced neoantigens offer new opportunities for engineered TCR-T cell therapies and neoantigen-based vaccines.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"611-613"},"PeriodicalIF":14.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337073","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
Tumor-draining lymph nodes - friend or foe during immune checkpoint therapy? 肿瘤引流淋巴结——免疫检查点治疗的朋友还是敌人？
IF 14.3 1区 医学
Trends in cancer Pub Date : 2025-07-01 Epub Date: 2025-05-09 DOI: 10.1016/j.trecan.2025.04.008
Janusz von Renesse, Mei-Chun Lin, Ping-Chih Ho
{"title":"Tumor-draining lymph nodes - friend or foe during immune checkpoint therapy?","authors":"Janusz von Renesse, Mei-Chun Lin, Ping-Chih Ho","doi":"10.1016/j.trecan.2025.04.008","DOIUrl":"10.1016/j.trecan.2025.04.008","url":null,"abstract":"<p><p>The pivotal role of tumor-draining lymph nodes (TDLNs) in supporting antitumor immunity and serving as sites for cancer metastasis presents a clinical challenge: eliminate tumors while preserving antitumor immune responses. In this article, we explore the initiation of tumor-specific immune responses within lymph nodes (LNs), the immunocompromised microenvironment induced by tumors within LNs, and the crucial involvement of TDLNs in immunotherapy. Additionally, we examine the clinical prospects of modifying surgical procedures or therapy sequences to enhance the efficacy of cancer treatment.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"676-690"},"PeriodicalIF":14.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050168","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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