Pub Date : 2024-06-04DOI: 10.1016/j.trecan.2024.04.004
Chris Abbosh, Darren Hodgson, Gary J. Doherty, Davina Gale, James R.M. Black, Leora Horn, Jorge S. Reis-Filho, Charles Swanton
Systemic treatment of resectable non-small cell lung cancer (NSCLC) is evolving with emerging neoadjuvant, perioperative, and adjuvant immunotherapy approaches. Circulating tumor DNA (ctDNA) detection at clinical diagnosis, during neoadjuvant therapy, or after resection may discern high-risk patients who might benefit from therapy escalation or switch. This Review summarizes translational implications of data supporting ctDNA-based risk determination in NSCLC and outstanding questions regarding ctDNA validity/utility as a prognostic biomarker. We discuss emerging ctDNA capabilities to refine clinical tumor–node–metastasis (TNM) staging in lung adenocarcinoma, ctDNA dynamics during neoadjuvant therapy for identifying patients deriving suboptimal benefit, and postoperative molecular residual disease (MRD) detection to escalate systemic therapy. Considering differential relapse characteristics in landmark MRD-negative/MRD-positive patients, we propose how ctDNA might integrate with pathological response data for optimal postoperative risk stratification.
{"title":"Implementing circulating tumor DNA as a prognostic biomarker in resectable non-small cell lung cancer","authors":"Chris Abbosh, Darren Hodgson, Gary J. Doherty, Davina Gale, James R.M. Black, Leora Horn, Jorge S. Reis-Filho, Charles Swanton","doi":"10.1016/j.trecan.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.04.004","url":null,"abstract":"<p>Systemic treatment of resectable non-small cell lung cancer (NSCLC) is evolving with emerging neoadjuvant, perioperative, and adjuvant immunotherapy approaches. Circulating tumor DNA (ctDNA) detection at clinical diagnosis, during neoadjuvant therapy, or after resection may discern high-risk patients who might benefit from therapy escalation or switch. This Review summarizes translational implications of data supporting ctDNA-based risk determination in NSCLC and outstanding questions regarding ctDNA validity/utility as a prognostic biomarker. We discuss emerging ctDNA capabilities to refine clinical tumor–node–metastasis (TNM) staging in lung adenocarcinoma, ctDNA dynamics during neoadjuvant therapy for identifying patients deriving suboptimal benefit, and postoperative molecular residual disease (MRD) detection to escalate systemic therapy. Considering differential relapse characteristics in landmark MRD-negative/MRD-positive patients, we propose how ctDNA might integrate with pathological response data for optimal postoperative risk stratification.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":"30 1","pages":""},"PeriodicalIF":18.4,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141258209","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 : 2024-06-04DOI: 10.1016/j.trecan.2024.05.004
David P. Turner, Robert A. Winn, Victoria J. Findlay
Social, environmental, and biological risk factors influence exposures to newly termed ‘biosocial determinants of health’. As molecular factors that lie at the intersection between lived experiences and individual biology, biosocial determinants may inform on the enduring complexity of cancer disparity across transdisciplinary studies.
{"title":"Biosocial determinants inform on enduring cancer disparities","authors":"David P. Turner, Robert A. Winn, Victoria J. Findlay","doi":"10.1016/j.trecan.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.05.004","url":null,"abstract":"<p>Social, environmental, and biological risk factors influence exposures to newly termed ‘biosocial determinants of health’. As molecular factors that lie at the intersection between lived experiences and individual biology, biosocial determinants may inform on the enduring complexity of cancer disparity across transdisciplinary studies.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":"53 1","pages":""},"PeriodicalIF":18.4,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141258180","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 : 2024-06-01Epub Date: 2024-03-21DOI: 10.1016/j.trecan.2024.02.007
Alex Miranda, Carl A Shirley, Russell W Jenkins
TANK-binding kinase 1 (TBK1) is a versatile serine/threonine protein kinase with established roles in innate immunity, metabolism, autophagy, cell death, and inflammation. While best known for its role in regulating innate immunity, TBK1 has emerged as a cancer cell-intrinsic immune evasion gene by virtue of its role in modulating cellular responses to inflammatory signals emanating from the immune system. Beyond its effect on cancer cells, TBK1 appears to regulate lymphoid and myeloid cells in the tumor immune microenvironment. In this review, we detail recent advances in our understanding of the tumor-intrinsic and -extrinsic roles and regulation of TBK1 in tumor immunity.
TANK 结合激酶 1(TBK1)是一种多功能丝氨酸/苏氨酸蛋白激酶,在先天性免疫、新陈代谢、自噬、细胞死亡和炎症中发挥着既定的作用。TBK1 因其在调节先天性免疫中的作用而闻名,但由于其在调节细胞对来自免疫系统的炎症信号的反应方面的作用,它已成为一种癌细胞内在免疫逃避基因。除了对癌细胞的影响,TBK1 似乎还能调节肿瘤免疫微环境中的淋巴细胞和骨髓细胞。在这篇综述中,我们将详细介绍最近在了解 TBK1 在肿瘤免疫中的内在和外在作用和调控方面取得的进展。
{"title":"Emerging roles of TBK1 in cancer immunobiology.","authors":"Alex Miranda, Carl A Shirley, Russell W Jenkins","doi":"10.1016/j.trecan.2024.02.007","DOIUrl":"10.1016/j.trecan.2024.02.007","url":null,"abstract":"<p><p>TANK-binding kinase 1 (TBK1) is a versatile serine/threonine protein kinase with established roles in innate immunity, metabolism, autophagy, cell death, and inflammation. While best known for its role in regulating innate immunity, TBK1 has emerged as a cancer cell-intrinsic immune evasion gene by virtue of its role in modulating cellular responses to inflammatory signals emanating from the immune system. Beyond its effect on cancer cells, TBK1 appears to regulate lymphoid and myeloid cells in the tumor immune microenvironment. In this review, we detail recent advances in our understanding of the tumor-intrinsic and -extrinsic roles and regulation of TBK1 in tumor immunity.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"531-540"},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190180","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}
Pub Date : 2024-06-01Epub Date: 2024-05-22DOI: 10.1016/j.trecan.2024.05.002
Philippa Vaughn-Beaucaire, Moon Jung Choi, Olin Liang, Sean E Lawler
Chimeric antigen receptor (CAR)-T cell therapy is emerging as a promising approach for improving outcomes in high-grade glioma. Here, we highlight three recent studies that reported safety and feasibility of intracranial CAR-T cell administration in patients with glioblastoma (GBM) as well as preliminary evidence of potential responses, supporting further investigations of this approach.
{"title":"Intracranial CAR-T cell delivery in glioblastoma patients.","authors":"Philippa Vaughn-Beaucaire, Moon Jung Choi, Olin Liang, Sean E Lawler","doi":"10.1016/j.trecan.2024.05.002","DOIUrl":"10.1016/j.trecan.2024.05.002","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy is emerging as a promising approach for improving outcomes in high-grade glioma. Here, we highlight three recent studies that reported safety and feasibility of intracranial CAR-T cell administration in patients with glioblastoma (GBM) as well as preliminary evidence of potential responses, supporting further investigations of this approach.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"478-480"},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082303","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 : 2024-06-01DOI: 10.1016/j.trecan.2024.05.005
Jacques Neefjes, Katerina Gurova, Jay Sarthy, Gábor Szabó, Steven Henikoff
Recent genome-wide analyses identified chromatin modifiers as one of the most frequently mutated classes of genes across all cancers. However, chemotherapies developed for cancers involving DNA damage remain the standard of care for chromatin-deranged malignancies. In this review we address this conundrum by establishing the concept of ‘chromatin damage’: the non-genetic damage to protein–DNA interactions induced by certain small molecules. We highlight anthracyclines, a class of chemotherapeutic agents ubiquitously applied in oncology, as an example of overlooked chromatin-targeting agents. We discuss our current understanding of this phenomenon and explore emerging chromatin-damaging agents as a basis for further studies to maximize their impact in modern cancer treatment.
{"title":"Chromatin as an old and new anticancer target","authors":"Jacques Neefjes, Katerina Gurova, Jay Sarthy, Gábor Szabó, Steven Henikoff","doi":"10.1016/j.trecan.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.05.005","url":null,"abstract":"<p>Recent genome-wide analyses identified chromatin modifiers as one of the most frequently mutated classes of genes across all cancers. However, chemotherapies developed for cancers involving DNA damage remain the standard of care for chromatin-deranged malignancies. In this review we address this conundrum by establishing the concept of ‘chromatin damage’: the non-genetic damage to protein–DNA interactions induced by certain small molecules. We highlight anthracyclines, a class of chemotherapeutic agents ubiquitously applied in oncology, as an example of overlooked chromatin-targeting agents. We discuss our current understanding of this phenomenon and explore emerging chromatin-damaging agents as a basis for further studies to maximize their impact in modern cancer treatment.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":"102 1","pages":""},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141196353","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 : 2024-06-01Epub Date: 2024-03-22DOI: 10.1016/j.trecan.2024.02.008
Victoria C Rayson, Michael A Harris, Peter Savas, Michael L Hun, Balaji Virassamy, Roberto Salgado, Sherene Loi
Triple-negative breast cancers (TNBCs) exhibit heightened T cell infiltration, contributing to an enhanced response to immune checkpoint blockade (ICB) compared with other subtypes. An immune-rich immune microenvironment correlates with improved prognosis in early and advanced TNBC. Combination chemotherapy and ICB is now the standard of care in early- and late-stage TNBC. Although programmed death ligand-1 (PD-L1) positivity predicts ICB response in advanced stages, its role in early-stage disease remains uncertain. Despite neoadjuvant ICB becoming common in early-stage TNBC, the necessity of adjuvant ICB after surgery remains unclear. Understanding the molecular basis of the immune response in breast cancer is vital for precise biomarkers for ICB and effective combination therapy strategies.
{"title":"The anti-cancer immune response in breast cancer: current and emerging biomarkers and treatments.","authors":"Victoria C Rayson, Michael A Harris, Peter Savas, Michael L Hun, Balaji Virassamy, Roberto Salgado, Sherene Loi","doi":"10.1016/j.trecan.2024.02.008","DOIUrl":"10.1016/j.trecan.2024.02.008","url":null,"abstract":"<p><p>Triple-negative breast cancers (TNBCs) exhibit heightened T cell infiltration, contributing to an enhanced response to immune checkpoint blockade (ICB) compared with other subtypes. An immune-rich immune microenvironment correlates with improved prognosis in early and advanced TNBC. Combination chemotherapy and ICB is now the standard of care in early- and late-stage TNBC. Although programmed death ligand-1 (PD-L1) positivity predicts ICB response in advanced stages, its role in early-stage disease remains uncertain. Despite neoadjuvant ICB becoming common in early-stage TNBC, the necessity of adjuvant ICB after surgery remains unclear. Understanding the molecular basis of the immune response in breast cancer is vital for precise biomarkers for ICB and effective combination therapy strategies.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"490-506"},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194648","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 : 2024-06-01Epub Date: 2024-03-29DOI: 10.1016/j.trecan.2024.03.003
Robin Demuynck, Yanou Engelen, André G Skirtach, Stefaan C De Smedt, Ine Lentacker, Dmitri V Krysko
Immunogenic cell death (ICD) is emerging as a key component of antitumor therapy that harnesses the immune system of the patient to combat cancer. In recent years, several efforts were made to improve the ICD-based therapies. Here, we discuss how nanomaterial-based strategies increase the efficacy of ICD and highlight their benefits and challenges.
{"title":"Nanomedicine to aid immunogenic cell death (ICD)-based anticancer therapy.","authors":"Robin Demuynck, Yanou Engelen, André G Skirtach, Stefaan C De Smedt, Ine Lentacker, Dmitri V Krysko","doi":"10.1016/j.trecan.2024.03.003","DOIUrl":"10.1016/j.trecan.2024.03.003","url":null,"abstract":"<p><p>Immunogenic cell death (ICD) is emerging as a key component of antitumor therapy that harnesses the immune system of the patient to combat cancer. In recent years, several efforts were made to improve the ICD-based therapies. Here, we discuss how nanomaterial-based strategies increase the efficacy of ICD and highlight their benefits and challenges.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"486-489"},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327203","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 : 2024-06-01Epub Date: 2024-03-19DOI: 10.1016/j.trecan.2024.02.011
Michaela Kuhlen, Thomas G Hofmann, Monika M Golas
Pathogenic variants (PVs) in DNA repair-linked adult-onset cancer predisposition genes, including double heterozygosity, are increasingly identified in pediatric patients with cancer. Their role in childhood cancer, however, remains poorly understood. Integrating comprehensive tumor analysis is integral for understanding the contribution of such PVs in cancer development and personalized cancer care.
在儿童癌症患者中,越来越多地发现了与 DNA 修复相关的成人发病癌症易感基因中的致病变异(PVs),包括双杂合子。然而,人们对它们在儿童癌症中的作用仍然知之甚少。综合全面的肿瘤分析是了解此类 PV 在癌症发展和个性化癌症治疗中的作用所不可或缺的。
{"title":"Puzzling phenomenon: adult-onset cancer predisposition and pediatric cancer.","authors":"Michaela Kuhlen, Thomas G Hofmann, Monika M Golas","doi":"10.1016/j.trecan.2024.02.011","DOIUrl":"10.1016/j.trecan.2024.02.011","url":null,"abstract":"<p><p>Pathogenic variants (PVs) in DNA repair-linked adult-onset cancer predisposition genes, including double heterozygosity, are increasingly identified in pediatric patients with cancer. Their role in childhood cancer, however, remains poorly understood. Integrating comprehensive tumor analysis is integral for understanding the contribution of such PVs in cancer development and personalized cancer care.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"481-485"},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176690","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 : 2024-06-01Epub Date: 2024-05-09DOI: 10.1016/j.trecan.2024.04.003
Max Julve, Mark P Lythgoe, James Larkin, Andrew J S Furness
The US Food and Drug Administration (FDA) approval of lifileucel, for advanced melanoma, represents the first cellular therapy to reach the clinic for solid cancers. Here, we summarise this landmark approval, consider the associated regulatory pathway, and evaluate the challenges that remain to ensure effective implementation of this advanced 'living' therapy.
{"title":"Lifileucel: the first cellular therapy approved for solid tumours.","authors":"Max Julve, Mark P Lythgoe, James Larkin, Andrew J S Furness","doi":"10.1016/j.trecan.2024.04.003","DOIUrl":"10.1016/j.trecan.2024.04.003","url":null,"abstract":"<p><p>The US Food and Drug Administration (FDA) approval of lifileucel, for advanced melanoma, represents the first cellular therapy to reach the clinic for solid cancers. Here, we summarise this landmark approval, consider the associated regulatory pathway, and evaluate the challenges that remain to ensure effective implementation of this advanced 'living' therapy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"475-477"},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899685","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 : 2024-06-01Epub Date: 2023-10-13DOI: 10.1016/j.trecan.2023.09.009
Kristin Huntoon, DaeYong Lee, Shiyan Dong, Abin Antony, Betty Y S Kim, Wen Jiang
{"title":"Targeting phagocytosis to enhance antitumor immunity: (Trends in Cancer, 9:8 p:650-665, 2023).","authors":"Kristin Huntoon, DaeYong Lee, Shiyan Dong, Abin Antony, Betty Y S Kim, Wen Jiang","doi":"10.1016/j.trecan.2023.09.009","DOIUrl":"10.1016/j.trecan.2023.09.009","url":null,"abstract":"","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"571"},"PeriodicalIF":18.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238976","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}