Cancer heterogeneity and plasticity最新文献_第2页

Regulation of Cancer Stem Cells in the Tumor Microenvironment. 肿瘤微环境中肿瘤干细胞的调控。

Cancer heterogeneity and plasticity Pub Date : 2025-01-01 Epub Date: 2025-09-26 DOI: 10.47248/chp2502040016

Aidan Li, Na Li, Yajing Yang, Linzhou Wang, Jessica Miao, Qi-En Wang

引用次数: 0

Molecular Characteristics, Heterogeneity, Plasticity, and Cell of Origin of Neuroendocrine Bladder Cancer. 神经内分泌膀胱癌的分子特征、异质性、可塑性和细胞起源。

Cancer heterogeneity and plasticity Pub Date : 2025-01-01 Epub Date: 2025-03-06 DOI: 10.47248/chp2502010005

Dongbo Xu, Qiang Li

{"title":"Molecular Characteristics, Heterogeneity, Plasticity, and Cell of Origin of Neuroendocrine Bladder Cancer.","authors":"Dongbo Xu, Qiang Li","doi":"10.47248/chp2502010005","DOIUrl":"10.47248/chp2502010005","url":null,"abstract":"Neuroendocrine bladder cancer (NEBC) is a rare but highly aggressive cancer, representing approximately 1% of urinary bladder cancer. The most common NEBC is small cell bladder cancer (SCBC), characterized by high rates of recurrence, chemotherapy resistance, and early mortality. SCBC is histologically identical to small cell lung cancer (SCLC) but remains significantly understudied. Advances in next-generation sequencing techniques have partially elucidated the molecular characteristics of NEBC and identified druggable targets. This review compiles recent studies on human NEBC samples, summarizing key findings on their genomic alterations and molecular subtyping. Notably, it highlights specific mutations in the TERT promoter and epigenetic modifiers in NEBC, as well as molecular subtyping based on lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. Furthermore, this review explores the significant tumor heterogeneity and cellular plasticity observed in NEBC and discusses its cell of origin and potential therapeutic targets (MET inhibitor or DLL3) identified by preclinical NEBC models. Emerging evidence suggests that NEBC may share a common origin with urothelial carcinoma (UC), arising from a UC precursor. Advancing our understanding of NEBC tumorigenesis and identifying druggable targets will enhance treatment outcomes for patients with NEBC.","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985787","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}

引用次数: 0

The three barriers senescent tumor cells must overcome to relapse. 衰老肿瘤细胞复发必须克服的三大障碍。

Cancer heterogeneity and plasticity Pub Date : 2025-01-01 Epub Date: 2025-08-04 DOI: 10.47248/chp2502030013

James G Jackson

{"title":"The three barriers senescent tumor cells must overcome to relapse.","authors":"James G Jackson","doi":"10.47248/chp2502030013","DOIUrl":"10.47248/chp2502030013","url":null,"abstract":"Tumor cells that enter senescence as a response to treatment can be permanently arrested or removed by the immune system, resulting in a favorable patient outcomes. Alternatively, many studies have now shown that, in some tumors, the senescent program enables tumor cell survival, persistence, and eventually relapse, resulting in poor patient outcomes. Whether senescence is a positive or negative factor is dependent on whether on a clonal population of cells overcomes three critical barriers. First, senescence must enable survival from the initial stress of treatment, such as DNA damage, by preventing apoptosis and/or mitotic catastrophe. Senescent cells are also frequently immunogenic, thus, a second barrier is the activation of programs of immune evasion, such as PD-L1 expression, that outweigh the immunogenic properties. Third, senescent cells must escape their rigid arrest to proliferate again. Studies over the years have experimentally addressed challenging questions related to relapse and senescence, but more research is needed, particularly in vivo. Here, we discuss critical studies investigating how tumor cells that enter senescence as a response to treatment overcome barriers to relapse.","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146128971","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}

引用次数: 0

A Hierarchy of Luminal Transcription Factors Defines AR Cistrome and Is Lost in Neuroendocrine Prostate Cancer. 在神经内分泌前列腺癌中，一系列的腔内转录因子定义了AR细胞限期和缺失。

Cancer heterogeneity and plasticity Pub Date : 2025-01-01 Epub Date: 2025-05-06 DOI: 10.47248/chp2502020008

Viriya Keo, Xiaodong Lu, Lourdes Brea, Xianglin Shi, Jindan Yu, Jonathan C Zhao

{"title":"A Hierarchy of Luminal Transcription Factors Defines AR Cistrome and Is Lost in Neuroendocrine Prostate Cancer.","authors":"Viriya Keo, Xiaodong Lu, Lourdes Brea, Xianglin Shi, Jindan Yu, Jonathan C Zhao","doi":"10.47248/chp2502020008","DOIUrl":"10.47248/chp2502020008","url":null,"abstract":"Androgen receptor (AR) is a hormonal transcription factor (TF) that binds to cis-regulatory elements of prostate lineage-specific genes to govern androgen response and progression of prostate cancer (PCa). This AR cistrome has been reported to be controlled by multiple chromatin-pioneering factors such as FOXA1, HOXB13, and GATA2. However, how these pioneer factors cooperate to regulate the AR cistrome remains unclear. Here, through comparative ChIP-seq analyses, we found that FOXA1 alone was sufficient to recruit AR to its binding sites regardless of H3K4me1. FOXA1 further enlisted HOXB13 and/or GATA2 to augment AR binding and enhancer activation, while HOXB13 and/or GATA2 alone were unable to recruit each other, nor AR. Moreover, HOXB13 knockdown attenuated AR and GATA2 expression and chromatin binding but failed to reprogram their cistromes, suggesting a role as a cofactor rather than a pioneer factor. During the neuroendocrine transformation (NET) of PCa, AR, GATA2, and HOXB13 were lost due to promoter hypermethylation, whereas FOXA1 was down-regulated by transcriptional repression. Lastly, through analyses of tissue microarrays, we confirmed that FOXA1 protein levels were drastically reduced in neuroendocrine PCa, as compared to AR-positive PCa. Therefore, our findings report a hierarchical network of TFs, pioneered by FOXA1 and facilitated by HOXB13 and GATA2, that defines lineage-specific AR cistrome and was lost during NET of PCa.","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329062","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}

引用次数: 0

The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer. 体内的特洛伊木马：乳腺癌的免疫逃避机制。

Cancer heterogeneity and plasticity Pub Date : 2025-01-01 Epub Date: 2025-12-05 DOI: 10.47248/chp2603010001

Biswajit Das, Charles W Winterbottom, Shaheen S Sikandar

{"title":"The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer.","authors":"Biswajit Das, Charles W Winterbottom, Shaheen S Sikandar","doi":"10.47248/chp2603010001","DOIUrl":"10.47248/chp2603010001","url":null,"abstract":"Breast cancer (BC) is the most common type of cancer among females, and the number of deaths due to BC has increased over the past few decades. BC is primarily categorized based on the receptor status of BC cells as hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+), and triple-negative BC (TNBC). These subtypes differ significantly in their treatment strategies, prognosis, immunogenic nature, and response to immunotherapy. TNBC is the most aggressive with a poor prognosis, but a subset of TNBCs that express programmed cell death ligand 1, have shown promising responses to immune checkpoint inhibitors. Across BC subtypes, distinct immune cell subsets remain active in the tumor immune microenvironment (TIME) that either inhibit or promote the growth of cancer. In isolation, it is challenging for cancer cells to thrive in presence of the body's immune system, however with the aid of other cells in the TIME, they can work together to evade immune detection by suppressing antigen presentation, modulating immune recognition markers, and recruiting immune-suppressive cells. In this review, we provide an overview of the BC immune evasion mechanisms and discuss aspects of immune evasion in relation to tumor heterogeneity and cellular plasticity. We also highlight successful clinical trials targeting immune-evasion markers and discuss the challenges and potential future directions for solving these problems.","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000313","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}

引用次数: 0

Advances in Single-Cell Techniques for Linking Phenotypes to Genotypes. 将表型与基因型联系起来的单细胞技术的进展。

Cancer heterogeneity and plasticity Pub Date : 2024-01-01 Epub Date: 2024-07-25 DOI: 10.47248/chp2401010004

Hsiao-Chun Chen, Yushu Ma, Jinxiong Cheng, Yu-Chih Chen

{"title":"Advances in Single-Cell Techniques for Linking Phenotypes to Genotypes.","authors":"Hsiao-Chun Chen, Yushu Ma, Jinxiong Cheng, Yu-Chih Chen","doi":"10.47248/chp2401010004","DOIUrl":"10.47248/chp2401010004","url":null,"abstract":"Single-cell analysis has become an essential tool in modern biological research, providing unprecedented insights into cellular behavior and heterogeneity. By examining individual cells, this approach surpasses conventional population-based methods, revealing critical variations in cellular states, responses to environmental cues, and molecular signatures. In the context of cancer, with its diverse cell populations, single-cell analysis is critical for investigating tumor evolution, metastasis, and therapy resistance. Understanding the phenotype-genotype relationship at the single-cell level is crucial for deciphering the molecular mechanisms driving tumor development and progression. This review highlights innovative strategies for selective cell isolation based on desired phenotypes, including robotic aspiration, laser detachment, microraft arrays, optical traps, and droplet-based microfluidic systems. These advanced tools facilitate high-throughput single-cell phenotypic analysis and sorting, enabling the identification and characterization of specific cell subsets, thereby advancing therapeutic innovations in cancer and other diseases.","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001648","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}

引用次数: 0

The molecular determinants of phenotypic plasticity in homeostasis and neoplasia. 内稳态和肿瘤中表型可塑性的分子决定因素。

Cancer heterogeneity and plasticity Pub Date : 2024-01-01 Epub Date: 2024-12-13 DOI: 10.47248/chp2401020010

Bradley Balk, David W Goodrich

引用次数: 0

Unmasking SMLR1: The hidden player in colorectal cancer's liver metastasis. 揭开 SMLR1 的神秘面纱：结直肠癌肝转移的隐藏角色

Cancer heterogeneity and plasticity Pub Date : 2024-01-01 Epub Date: 2024-07-18 DOI: 10.47248/chp2401010002

Xiaozhuo Liu

引用次数: 0

Cancer Heterogeneity and Plasticity - A new journal dedicated to understanding cancer cell states and interactions with the tumor microenvironment. Cancer Heterogeneity and Plasticity（《癌症异质性与可塑性》）--一本致力于了解癌细胞状态以及与肿瘤微环境相互作用的新期刊。

Cancer heterogeneity and plasticity Pub Date : 2024-01-01 Epub Date: 2024-07-18 DOI: 10.47248/chp2401010001

Dean G Tang

引用次数: 0

Treatment-induced stemness and lineage plasticity in driving prostate cancer therapy resistance. 治疗诱导的干性和血统可塑性是前列腺癌耐药性的驱动因素。

Cancer heterogeneity and plasticity Pub Date : 2024-01-01 Epub Date: 2024-08-25 DOI: 10.47248/chp2401010005

Anmbreen Jamroze, Xiaozhuo Liu, Dean G Tang

{"title":"Treatment-induced stemness and lineage plasticity in driving prostate cancer therapy resistance.","authors":"Anmbreen Jamroze, Xiaozhuo Liu, Dean G Tang","doi":"10.47248/chp2401010005","DOIUrl":"10.47248/chp2401010005","url":null,"abstract":"Most human cancers are heterogeneous consisting of cancer cells at different epigenetic and transcriptional states and with distinct phenotypes, functions, and drug sensitivities. This inherent cancer cell heterogeneity contributes to tumor resistance to clinical treatment, especially the molecularly targeted therapies such as tyrosine kinase inhibitors (TKIs) and androgen receptor signaling inhibitors (ARSIs). Therapeutic interventions, in turn, induce lineage plasticity (also called lineage infidelity) in cancer cells that also drives therapy resistance. In this Perspective, we focus our discussions on cancer cell lineage plasticity manifested as treatment-induced switching of epithelial cancer cells to basal/stem-like, mesenchymal, and neural lineages. We employ prostate cancer (PCa) as the prime example to highlight ARSI-induced lineage plasticity during and towards development of castration-resistant PCa (CRPC). We further discuss how the tumor microenvironment (TME) influences therapy-induced lineage plasticity. Finally, we offer an updated summary on the regulators and mechanisms driving cancer cell lineage infidelity, which should be therapeutically targeted to extend the therapeutic window and improve patients' survival.","PeriodicalId":520023,"journal":{"name":"Cancer heterogeneity and plasticity","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373999","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}

引用次数: 0