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":null,"pages":null},"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":null,"pages":null},"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}
Pub Date : 2024-10-25DOI: 10.1016/j.trecan.2024.10.001
Jerry Tyler DeWitt, Megha Raghunathan, Svasti Haricharan
DNA damage repair (DDR) proteins are well recognized as guardians of the genome that are frequently lost during malignant transformation of normal cells across cancer types. To date, their tumor suppressor functions have been generally regarded as a consequence of their roles in maintaining genomic stability: more genomic instability increases the risk of oncogenic transformation events. However, recent discoveries centering around DNA mismatch repair (MMR) proteins suggest a broader impact of the loss of DDR proteins on cellular processes beyond genomic instability. Here, we explore the clinical implications of nonrepair roles for DDR proteins, using the growing evidence supporting roles for DNA MMR proteins in cell cycle and apoptosis regulation, metabolic function, the cellular secretome, and immunomodulation.
DNA 损伤修复(DDR)蛋白被公认为基因组的守护者,在正常细胞向各种癌症类型恶性转化的过程中,它们经常丢失。迄今为止,人们普遍认为它们的抑瘤功能是维持基因组稳定性的结果:基因组越不稳定,致癌转化的风险就越大。然而,最近围绕 DNA 错配修复(MMR)蛋白的发现表明,除基因组不稳定性外,DDR 蛋白的缺失还会对细胞过程产生更广泛的影响。在这里,我们利用越来越多的证据支持 DNA MMR 蛋白在细胞周期和凋亡调节、代谢功能、细胞分泌组和免疫调节中的作用,探讨 DDR 蛋白的非修复作用对临床的影响。
{"title":"Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.","authors":"Jerry Tyler DeWitt, Megha Raghunathan, Svasti Haricharan","doi":"10.1016/j.trecan.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.001","url":null,"abstract":"<p><p>DNA damage repair (DDR) proteins are well recognized as guardians of the genome that are frequently lost during malignant transformation of normal cells across cancer types. To date, their tumor suppressor functions have been generally regarded as a consequence of their roles in maintaining genomic stability: more genomic instability increases the risk of oncogenic transformation events. However, recent discoveries centering around DNA mismatch repair (MMR) proteins suggest a broader impact of the loss of DDR proteins on cellular processes beyond genomic instability. Here, we explore the clinical implications of nonrepair roles for DDR proteins, using the growing evidence supporting roles for DNA MMR proteins in cell cycle and apoptosis regulation, metabolic function, the cellular secretome, and immunomodulation.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569617","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 : 2024-10-24DOI: 10.1016/j.trecan.2024.10.006
Meggy Suarez-Carmona, Niels Halama
Neoadjuvant immune checkpoint inhibition (ICI) is a new approach to treat patients with colorectal cancer (CRC). The effects of combined neoadjuvant ICI in locally advanced, DNA mismatch repair (dMMR)-deficient/microsatellite instable (MSI) CRC were recently reported by de Gooyer et al. from the NICHE-3 trial. Further studies will determine whether these impressive pathological responses lead to long-term clinical benefit.
{"title":"Neoadjuvant combination immunotherapy in MSI/dMMR colorectal cancer.","authors":"Meggy Suarez-Carmona, Niels Halama","doi":"10.1016/j.trecan.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.006","url":null,"abstract":"<p><p>Neoadjuvant immune checkpoint inhibition (ICI) is a new approach to treat patients with colorectal cancer (CRC). The effects of combined neoadjuvant ICI in locally advanced, DNA mismatch repair (dMMR)-deficient/microsatellite instable (MSI) CRC were recently reported by de Gooyer et al. from the NICHE-3 trial. Further studies will determine whether these impressive pathological responses lead to long-term clinical benefit.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508858","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}
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.
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-24","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}
Pub Date : 2024-10-21DOI: 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
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.
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-21","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}
Pub Date : 2024-10-10DOI: 10.1016/j.trecan.2024.09.007
Santiago Haase, Stephen Carney, Maria Luisa Varela, Devarshi Mukherji, Ziwen Zhu, Yingxiang Li, Felipe J Nuñez, Pedro R Lowenstein, Maria G Castro
Brain tumors in children and adults differ greatly in patient outcomes and responses to radiotherapy and chemotherapy. Moreover, the prevalence of recurrent mutations in histones and chromatin regulatory proteins in pediatric and young adult gliomas suggests that the chromatin landscape is rewired to support oncogenic programs. These early somatic mutations dysregulate widespread genomic loci by altering the distribution of histone post-translational modifications (PTMs) and, in consequence, causing changes in chromatin accessibility and in the histone code, leading to gene transcriptional changes. We review how distinct chromatin imbalances in glioma subtypes impact on oncogenic features such as cellular fate, proliferation, immune landscape, and radio resistance. Understanding these mechanisms of epigenetic dysregulation carries substantial implications for advancing targeted epigenetic therapies.
{"title":"Epigenetic reprogramming in pediatric gliomas: from molecular mechanisms to therapeutic implications.","authors":"Santiago Haase, Stephen Carney, Maria Luisa Varela, Devarshi Mukherji, Ziwen Zhu, Yingxiang Li, Felipe J Nuñez, Pedro R Lowenstein, Maria G Castro","doi":"10.1016/j.trecan.2024.09.007","DOIUrl":"10.1016/j.trecan.2024.09.007","url":null,"abstract":"<p><p>Brain tumors in children and adults differ greatly in patient outcomes and responses to radiotherapy and chemotherapy. Moreover, the prevalence of recurrent mutations in histones and chromatin regulatory proteins in pediatric and young adult gliomas suggests that the chromatin landscape is rewired to support oncogenic programs. These early somatic mutations dysregulate widespread genomic loci by altering the distribution of histone post-translational modifications (PTMs) and, in consequence, causing changes in chromatin accessibility and in the histone code, leading to gene transcriptional changes. We review how distinct chromatin imbalances in glioma subtypes impact on oncogenic features such as cellular fate, proliferation, immune landscape, and radio resistance. Understanding these mechanisms of epigenetic dysregulation carries substantial implications for advancing targeted epigenetic therapies.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406950","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 : 2024-10-09DOI: 10.1016/j.trecan.2024.09.006
Xinran An, Justin Paoloni, Yuseong Oh, Jamie B Spangler
Growth factors signal through engagement and activation of their respective cell surface receptors to choreograph an array of cellular functions, including proliferation, growth, repair, migration, differentiation, and survival. Because of their vital role in determining cell fate and maintaining homeostasis, dysregulation of growth factor pathways leads to the development and/or progression of disease, particularly in the context of cancer. Exciting advances in protein engineering technologies have enabled innovative strategies to redesign naturally occurring growth factor ligands and receptors as targeted therapeutics. We review growth factor protein engineering efforts, including affinity modulation, molecular fusion, the design of decoy receptors, dual specificity constructs, and vaccines. Collectively, these approaches are catapulting next-generation drugs to treat cancer and a host of other conditions.
{"title":"Engineering growth factor ligands and receptors for therapeutic innovation.","authors":"Xinran An, Justin Paoloni, Yuseong Oh, Jamie B Spangler","doi":"10.1016/j.trecan.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.09.006","url":null,"abstract":"<p><p>Growth factors signal through engagement and activation of their respective cell surface receptors to choreograph an array of cellular functions, including proliferation, growth, repair, migration, differentiation, and survival. Because of their vital role in determining cell fate and maintaining homeostasis, dysregulation of growth factor pathways leads to the development and/or progression of disease, particularly in the context of cancer. Exciting advances in protein engineering technologies have enabled innovative strategies to redesign naturally occurring growth factor ligands and receptors as targeted therapeutics. We review growth factor protein engineering efforts, including affinity modulation, molecular fusion, the design of decoy receptors, dual specificity constructs, and vaccines. Collectively, these approaches are catapulting next-generation drugs to treat cancer and a host of other conditions.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401444","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 : 2024-10-05DOI: 10.1016/j.trecan.2024.09.005
Venkata Narasimha Kadali, Ofer Shoshani
Gene amplification in the form of extrachromosomal DNA (ecDNA) or intrachromosomal homogenous staining regions (HSRs) is an emerging hallmark in cancer. Recent studies implicate abnormal nuclear structures in the biogenesis and evolution of amplified DNA. Here, we discuss how the interplay between aberrant nuclei and gene amplification drives cancer therapy resistance and metastasis.
染色体外 DNA(ecDNA)或染色体内同源染色区(HSR)形式的基因扩增是癌症的一个新特征。最近的研究表明,核结构异常与扩增 DNA 的生物发生和进化有关。在此,我们将讨论异常细胞核与基因扩增之间的相互作用是如何驱动癌症耐药性和转移的。
{"title":"Aberrant nuclei with amplified DNA in cancer.","authors":"Venkata Narasimha Kadali, Ofer Shoshani","doi":"10.1016/j.trecan.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.09.005","url":null,"abstract":"<p><p>Gene amplification in the form of extrachromosomal DNA (ecDNA) or intrachromosomal homogenous staining regions (HSRs) is an emerging hallmark in cancer. Recent studies implicate abnormal nuclear structures in the biogenesis and evolution of amplified DNA. Here, we discuss how the interplay between aberrant nuclei and gene amplification drives cancer therapy resistance and metastasis.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381736","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 : 2024-10-01Epub Date: 2024-08-19DOI: 10.1016/j.trecan.2024.07.008
Esther Redin, Álvaro Quintanal-Villalonga, Charles M Rudin
Small cell lung cancer (SCLC) is a devastating disease with high proliferative and metastatic capacity. SCLC has been classified into molecular subtypes based on differential expression of lineage-defining transcription factors. Recent studies have proposed new subtypes that are based on both tumor-intrinsic and -extrinsic factors. SCLC demonstrates substantial intratumoral subtype heterogeneity characterized by highly plastic transcriptional states, indicating that the initially dominant subtype can shift during disease progression and in association with resistance to therapy. Strategies to promote or constrain plasticity and cell fate transitions have nominated novel targets that could prompt the development of more durably effective therapies for patients with SCLC. In this review, we describe the latest advances in SCLC subtype classification and their biological and clinical implications.
{"title":"Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity.","authors":"Esther Redin, Álvaro Quintanal-Villalonga, Charles M Rudin","doi":"10.1016/j.trecan.2024.07.008","DOIUrl":"10.1016/j.trecan.2024.07.008","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is a devastating disease with high proliferative and metastatic capacity. SCLC has been classified into molecular subtypes based on differential expression of lineage-defining transcription factors. Recent studies have proposed new subtypes that are based on both tumor-intrinsic and -extrinsic factors. SCLC demonstrates substantial intratumoral subtype heterogeneity characterized by highly plastic transcriptional states, indicating that the initially dominant subtype can shift during disease progression and in association with resistance to therapy. Strategies to promote or constrain plasticity and cell fate transitions have nominated novel targets that could prompt the development of more durably effective therapies for patients with SCLC. In this review, we describe the latest advances in SCLC subtype classification and their biological and clinical implications.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009523","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}