The Hippo pathway has emerged as a critical player in both cancers and targeted therapy resistance. Recent drug discovery efforts have led to the development of TEAD inhibitors, several of which have already progressed to the clinic. To truly leverage their potential as anticancer therapeutics, safety considerations, particularly in regard to the kidney, warrant additional investigation. This review explores the Hippo pathway's role in cancers, its therapeutic potential, role in kidney development, and the need to evaluate the best strategies to translate its clinical application for long-term patient benefit.
{"title":"Targeting the Hippo pathway in cancer: kidney toxicity as a class effect of TEAD inhibitors?","authors":"Sayantanee Paul, Jessica Sims, Trang Pham, Anwesha Dey","doi":"10.1016/j.trecan.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.004","url":null,"abstract":"<p><p>The Hippo pathway has emerged as a critical player in both cancers and targeted therapy resistance. Recent drug discovery efforts have led to the development of TEAD inhibitors, several of which have already progressed to the clinic. To truly leverage their potential as anticancer therapeutics, safety considerations, particularly in regard to the kidney, warrant additional investigation. This review explores the Hippo pathway's role in cancers, its therapeutic potential, role in kidney development, and the need to evaluate the best strategies to translate its clinical application for long-term patient benefit.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628777","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}
Pub Date : 2024-11-06DOI: 10.1016/j.trecan.2024.10.005
Stanislav Drapela, Bruna M Garcia, Ana P Gomes, Ana Luísa Correia
Cancer dormancy is a phenomenon defined by the entry of cancer cells into a reversible quiescent, nonproliferative state, and represents an essential part of the metastatic cascade responsible for cancer recurrence and mortality. Emerging evidence suggests that metabolic reprogramming plays a pivotal role in enabling entry, maintenance, and exit from dormancy in the face of the different environments of the metastatic cascade. Here, we review the current literature to understand the dynamics of metabolism during dormancy, highlighting its fine-tuning by the host micro- and macroenvironment, and put forward the importance of identifying metabolic vulnerabilities of the dormant state as therapeutic targets to eradicate recurrent disease.
{"title":"Metabolic landscape of disseminated cancer dormancy.","authors":"Stanislav Drapela, Bruna M Garcia, Ana P Gomes, Ana Luísa Correia","doi":"10.1016/j.trecan.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.005","url":null,"abstract":"<p><p>Cancer dormancy is a phenomenon defined by the entry of cancer cells into a reversible quiescent, nonproliferative state, and represents an essential part of the metastatic cascade responsible for cancer recurrence and mortality. Emerging evidence suggests that metabolic reprogramming plays a pivotal role in enabling entry, maintenance, and exit from dormancy in the face of the different environments of the metastatic cascade. Here, we review the current literature to understand the dynamics of metabolism during dormancy, highlighting its fine-tuning by the host micro- and macroenvironment, and put forward the importance of identifying metabolic vulnerabilities of the dormant state as therapeutic targets to eradicate recurrent disease.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606455","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}
Pub Date : 2024-11-01Epub Date: 2024-09-06DOI: 10.1016/j.trecan.2024.08.004
Claudia Galassi, Manel Esteller, Ilio Vitale, Lorenzo Galluzzi
Cancer stem cells (CSCs) are a poorly differentiated population of malignant cells that (at least in some neoplasms) is responsible for tumor progression, resistance to therapy, and disease relapse. According to a widely accepted model, all stages of cancer progression involve the ability of neoplastic cells to evade recognition or elimination by the host immune system. In line with this notion, CSCs are not only able to cope with environmental and therapy-elicited stress better than their more differentiated counterparts but also appear to better evade tumor-targeting immune responses. We summarize epigenetic modifications of DNA and histones through which CSCs evade immune recognition or elimination, and propose that such alterations constitute promising therapeutic targets to increase the sensitivity of some malignancies to immunotherapy.
{"title":"Epigenetic control of immunoevasion in cancer stem cells.","authors":"Claudia Galassi, Manel Esteller, Ilio Vitale, Lorenzo Galluzzi","doi":"10.1016/j.trecan.2024.08.004","DOIUrl":"10.1016/j.trecan.2024.08.004","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a poorly differentiated population of malignant cells that (at least in some neoplasms) is responsible for tumor progression, resistance to therapy, and disease relapse. According to a widely accepted model, all stages of cancer progression involve the ability of neoplastic cells to evade recognition or elimination by the host immune system. In line with this notion, CSCs are not only able to cope with environmental and therapy-elicited stress better than their more differentiated counterparts but also appear to better evade tumor-targeting immune responses. We summarize epigenetic modifications of DNA and histones through which CSCs evade immune recognition or elimination, and propose that such alterations constitute promising therapeutic targets to increase the sensitivity of some malignancies to immunotherapy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1052-1071"},"PeriodicalIF":14.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146405","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}
Pub Date : 2024-11-01Epub Date: 2024-08-31DOI: 10.1016/j.trecan.2024.08.001
Lillian M Perez, Smrruthi V Venugopal, Anna St Martin, Stephen J Freedland, Dolores Di Vizio, Michael R Freeman
Dynamic alterations in cellular phenotypes during cancer progression are attributed to a phenomenon known as 'lineage plasticity'. This process is associated with therapeutic resistance and involves concurrent shifts in metabolic states that facilitate adaptation to various stressors inherent in malignant growth. Certain metabolites also serve as synthetic reservoirs for chromatin modification, thus linking metabolic states with epigenetic regulation. There remains a critical need to understand the mechanisms that converge on lineage plasticity and metabolic reprogramming to prevent the emergence of lethal disease. This review attempts to offer an overview of our current understanding of the interplay between metabolic reprogramming and lineage plasticity in the context of cancer, highlighting the intersecting drivers of cancer hallmarks, with an emphasis on solid tumors.
{"title":"Mechanisms governing lineage plasticity and metabolic reprogramming in cancer.","authors":"Lillian M Perez, Smrruthi V Venugopal, Anna St Martin, Stephen J Freedland, Dolores Di Vizio, Michael R Freeman","doi":"10.1016/j.trecan.2024.08.001","DOIUrl":"10.1016/j.trecan.2024.08.001","url":null,"abstract":"<p><p>Dynamic alterations in cellular phenotypes during cancer progression are attributed to a phenomenon known as 'lineage plasticity'. This process is associated with therapeutic resistance and involves concurrent shifts in metabolic states that facilitate adaptation to various stressors inherent in malignant growth. Certain metabolites also serve as synthetic reservoirs for chromatin modification, thus linking metabolic states with epigenetic regulation. There remains a critical need to understand the mechanisms that converge on lineage plasticity and metabolic reprogramming to prevent the emergence of lethal disease. This review attempts to offer an overview of our current understanding of the interplay between metabolic reprogramming and lineage plasticity in the context of cancer, highlighting the intersecting drivers of cancer hallmarks, with an emphasis on solid tumors.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1009-1022"},"PeriodicalIF":14.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112410","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}
Pub Date : 2024-11-01Epub Date: 2024-09-04DOI: 10.1016/j.trecan.2024.08.006
Xinyuan Zhou, Binyu Shi, Gang Huang, Jianjun Liu, Weijun Wei
Molecular imaging of cancer is a collaborative endeavor, uniting scientists and physicians from diverse fields. Such collaboration is actively developing and translating cutting-edge molecular imaging approaches to enhance the diagnostic landscape of human malignancies. The advent of positron emission tomography (PET) and PET imaging tracers has realized non-invasive target annotation and tumor characterization at the molecular level. In surgical procedures, novel imaging techniques, such as fluorescence or Cherenkov luminescence, help identify tumors and enhance surgical precision. Simultaneously, progress in imaging equipment, innovative algorithms, and artificial intelligence has opened avenues for next-generation cancer screening and imaging, augmenting the efficiency and accuracy of cancer diagnosis. In this review, we provide a panorama of molecular cancer imaging and ongoing developments in the field.
癌症分子成像是一项合作性工作,它将来自不同领域的科学家和医生团结在一起。这种合作正在积极开发和转化最前沿的分子成像方法,以改善人类恶性肿瘤的诊断状况。正电子发射断层扫描(PET)和 PET 成像示踪剂的出现实现了分子水平的无创靶标标注和肿瘤特征描述。在外科手术中,荧光或切伦科夫发光等新型成像技术有助于识别肿瘤并提高手术精确度。与此同时,成像设备、创新算法和人工智能的进步为下一代癌症筛查和成像开辟了道路,提高了癌症诊断的效率和准确性。在这篇综述中,我们将介绍癌症分子成像的全景以及该领域的持续发展。
{"title":"Trends in cancer imaging.","authors":"Xinyuan Zhou, Binyu Shi, Gang Huang, Jianjun Liu, Weijun Wei","doi":"10.1016/j.trecan.2024.08.006","DOIUrl":"10.1016/j.trecan.2024.08.006","url":null,"abstract":"<p><p>Molecular imaging of cancer is a collaborative endeavor, uniting scientists and physicians from diverse fields. Such collaboration is actively developing and translating cutting-edge molecular imaging approaches to enhance the diagnostic landscape of human malignancies. The advent of positron emission tomography (PET) and PET imaging tracers has realized non-invasive target annotation and tumor characterization at the molecular level. In surgical procedures, novel imaging techniques, such as fluorescence or Cherenkov luminescence, help identify tumors and enhance surgical precision. Simultaneously, progress in imaging equipment, innovative algorithms, and artificial intelligence has opened avenues for next-generation cancer screening and imaging, augmenting the efficiency and accuracy of cancer diagnosis. In this review, we provide a panorama of molecular cancer imaging and ongoing developments in the field.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1023-1037"},"PeriodicalIF":14.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133893","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}
Pub Date : 2024-11-01Epub Date: 2024-10-01DOI: 10.1016/j.trecan.2024.09.009
Esmeralda García-Torralba, Lorenzo Galluzzi, Aitziber Buqué
The impact of tumor-infiltrating B cells on breast cancer (BRCA) outcomes remains poorly understood. Recent findings from Yang et al. identify an atypical, clonally expanded population of activated Fc receptor-like 4 (FCRL4)+ B cells that is associated with improved overall survival in patients affected by various tumor types, including BRCA.
人们对肿瘤浸润性 B 细胞对乳腺癌(BRCA)预后的影响仍然知之甚少。Yang等人的最新研究发现,活化的Fc受体样4(FCRL4)+B细胞是一种非典型、克隆性扩增的细胞群,它与包括BRCA在内的各种肿瘤患者总生存率的提高有关。
{"title":"Prognostic value of atypical B cells in breast cancer.","authors":"Esmeralda García-Torralba, Lorenzo Galluzzi, Aitziber Buqué","doi":"10.1016/j.trecan.2024.09.009","DOIUrl":"10.1016/j.trecan.2024.09.009","url":null,"abstract":"<p><p>The impact of tumor-infiltrating B cells on breast cancer (BRCA) outcomes remains poorly understood. Recent findings from Yang et al. identify an atypical, clonally expanded population of activated Fc receptor-like 4 (FCRL4)<sup>+</sup> B cells that is associated with improved overall survival in patients affected by various tumor types, including BRCA.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"990-991"},"PeriodicalIF":14.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366683","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}
Pub Date : 2024-11-01Epub Date: 2024-10-02DOI: 10.1016/j.trecan.2024.08.003
Adrian L Harris, David J Kerr, Francesco Pezzella, Domenico Ribatti
The classic cancer hallmark, inducing angiogenesis, was born out of the long-held notion that tumours could grow only if new vessels were formed. The attempts, based on this premise, to therapeutically restrain angiogenesis in hopes of controlling tumour growth have been less effective than expected. This is partly because primary and metastatic tumours can grow without angiogenesis. The discovery of nonangiogenic cancers and the mechanisms they use to exploit normal vessels, called 'vessel co-option,' has opened a new field in cancer biology. Consequently, the cancer hallmark, 'inducing angiogenesis,' has been modified to 'inducing or accessing vasculature.'
{"title":"Accessing the vasculature in cancer: revising an old hallmark.","authors":"Adrian L Harris, David J Kerr, Francesco Pezzella, Domenico Ribatti","doi":"10.1016/j.trecan.2024.08.003","DOIUrl":"10.1016/j.trecan.2024.08.003","url":null,"abstract":"<p><p>The classic cancer hallmark, inducing angiogenesis, was born out of the long-held notion that tumours could grow only if new vessels were formed. The attempts, based on this premise, to therapeutically restrain angiogenesis in hopes of controlling tumour growth have been less effective than expected. This is partly because primary and metastatic tumours can grow without angiogenesis. The discovery of nonangiogenic cancers and the mechanisms they use to exploit normal vessels, called 'vessel co-option,' has opened a new field in cancer biology. Consequently, the cancer hallmark, 'inducing angiogenesis,' has been modified to 'inducing or accessing vasculature.'</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1038-1051"},"PeriodicalIF":14.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366682","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}
Pub Date : 2024-11-01Epub Date: 2024-10-02DOI: 10.1016/j.trecan.2024.09.008
Dhanashree Mundhe, Neta Erez
New findings by Watson et al. demonstrate that therapy-induced inflammation and fibrosis potentiate glioblastoma recurrence. Post-treatment fibrotic niches shielded surviving tumor cells from immune surveillance, supported their persistence in a dormant state, and enabled rebound growth. Timely inhibition of inflammation and scarring attenuated recurrence, encouraging the use of new combinatorial approaches in glioblastoma therapy.
{"title":"Time to heal: inhibiting fibrosis prevents glioblastoma recurrence.","authors":"Dhanashree Mundhe, Neta Erez","doi":"10.1016/j.trecan.2024.09.008","DOIUrl":"10.1016/j.trecan.2024.09.008","url":null,"abstract":"<p><p>New findings by Watson et al. demonstrate that therapy-induced inflammation and fibrosis potentiate glioblastoma recurrence. Post-treatment fibrotic niches shielded surviving tumor cells from immune surveillance, supported their persistence in a dormant state, and enabled rebound growth. Timely inhibition of inflammation and scarring attenuated recurrence, encouraging the use of new combinatorial approaches in glioblastoma therapy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"987-989"},"PeriodicalIF":14.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366684","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}
Pub Date : 2024-10-30DOI: 10.1016/j.trecan.2024.10.003
Luana Schito, Sergio Rey-Keim
Gene expression regulation in hypoxic tumor microenvironments is mediated by O2 responsive transcription factors (O2R-TFs), fine-tuning cancer cell metabolic demand for O2 according to its availability. Here, we discuss key O2R-TFs and emerging artificial intelligence (AI)-based applications suitable for the interrogation of O2R-TF relationships specifying cancer cell metabolic adaptations to hypoxia.
{"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":"https://doi.org/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":""},"PeriodicalIF":14.3,"publicationDate":"2024-10-30","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}
Pub Date : 2024-10-29DOI: 10.1016/j.trecan.2024.09.011
Hery Urra, Raúl Aravena, Lucas González-Johnson, Claudio Hetz
The tumor microenvironment (TME) represents a dynamic network of cancer cells, stromal cells, immune mediators, and extracellular matrix components, crucial for cancer progression. Stress conditions such as oncogene activation, nutrient deprivation, and hypoxia disrupt the endoplasmic reticulum (ER), activating the unfolded protein response (UPR), the main adaptive mechanism to restore ER function. The UPR regulates cancer progression by engaging cell-autonomous and cell-non-autonomous mechanisms, reprogramming the stroma and promoting immune evasion, angiogenesis, and invasion. This review explores the role of UPR beyond cancer cells, focusing on how ER stress signaling reshapes the TME, supporting tumor growth. The therapeutic potential of targeting the UPR is also discussed.
肿瘤微环境(TME)是由癌细胞、基质细胞、免疫介质和细胞外基质成分组成的动态网络,对癌症的进展至关重要。癌基因激活、营养匮乏和缺氧等应激条件会破坏内质网(ER),激活未折叠蛋白反应(UPR),这是恢复ER功能的主要适应机制。UPR 通过调动细胞自主和细胞非自主机制、重塑基质以及促进免疫逃避、血管生成和侵袭来调控癌症进展。本综述探讨了 UPR 在癌细胞之外的作用,重点关注 ER 应激信号如何重塑 TME,从而支持肿瘤生长。此外,还讨论了针对 UPR 的治疗潜力。
{"title":"The UPRising connection between endoplasmic reticulum stress and the tumor microenvironment.","authors":"Hery Urra, Raúl Aravena, Lucas González-Johnson, Claudio Hetz","doi":"10.1016/j.trecan.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.09.011","url":null,"abstract":"<p><p>The tumor microenvironment (TME) represents a dynamic network of cancer cells, stromal cells, immune mediators, and extracellular matrix components, crucial for cancer progression. Stress conditions such as oncogene activation, nutrient deprivation, and hypoxia disrupt the endoplasmic reticulum (ER), activating the unfolded protein response (UPR), the main adaptive mechanism to restore ER function. The UPR regulates cancer progression by engaging cell-autonomous and cell-non-autonomous mechanisms, reprogramming the stroma and promoting immune evasion, angiogenesis, and invasion. This review explores the role of UPR beyond cancer cells, focusing on how ER stress signaling reshapes the TME, supporting tumor growth. The therapeutic potential of targeting the UPR is also discussed.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547714","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}