Suman Paul, Maximilian F. Konig, Drew M. Pardoll, Chetan Bettegowda, Nickolas Papadopoulos, Katharine M. Wright, Sandra B. Gabelli, Mitchell Ho, Andrea van Elsas, Shibin Zhou
{"title":"Cancer therapy with antibodies","authors":"Suman Paul, Maximilian F. Konig, Drew M. Pardoll, Chetan Bettegowda, Nickolas Papadopoulos, Katharine M. Wright, Sandra B. Gabelli, Mitchell Ho, Andrea van Elsas, Shibin Zhou","doi":"10.1038/s41568-024-00690-x","DOIUrl":"10.1038/s41568-024-00690-x","url":null,"abstract":"The greatest challenge in cancer therapy is to eradicate cancer cells with minimal damage to normal cells. Targeted therapy has been developed to meet that challenge, showing a substantially increased therapeutic index compared with conventional cancer therapies. Antibodies are important members of the family of targeted therapeutic agents because of their extraordinarily high specificity to the target antigens. Therapeutic antibodies use a range of mechanisms that directly or indirectly kill the cancer cells. Early antibodies were developed to directly antagonize targets on cancer cells. This was followed by advancements in linker technologies that allowed the production of antibody–drug conjugates (ADCs) that guide cytotoxic payloads to the cancer cells. Improvement in our understanding of the biology of T cells led to the production of immune checkpoint-inhibiting antibodies that indirectly kill the cancer cells through activation of the T cells. Even more recently, bispecific antibodies were synthetically designed to redirect the T cells of a patient to kill the cancer cells. In this Review, we summarize the different approaches used by therapeutic antibodies to target cancer cells. We discuss their mechanisms of action, the structural basis for target specificity, clinical applications and the ongoing research to improve efficacy and reduce toxicity. In this Review, Paul et al. provide an overview of therapeutic antibodies as an important modality in cancer therapy today. They summarize the different approaches used by antibodies to target cancer cells including those of immune checkpoint inhibitors, bispecific antibodies and antibody–drug conjugates, as well as describing current strategies aimed at improving their efficacy and reducing toxicities.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"399-426"},"PeriodicalIF":78.5,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915109","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}
{"title":"Right ON target: a new RAS-GTP inhibitor","authors":"Daniela Senft","doi":"10.1038/s41568-024-00703-9","DOIUrl":"10.1038/s41568-024-00703-9","url":null,"abstract":"Two studies published concurrently in Nature report the development and preclinical activity of RMC-7977, a multi-selective inhibitor targeting the active, GTP-bound form of RAS.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"361-361"},"PeriodicalIF":78.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904439","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}
{"title":"AACR 2024","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00701-x","DOIUrl":"10.1038/s41568-024-00701-x","url":null,"abstract":"The annual American Association for Cancer Research (AACR) meeting provides a platform for scientists, clinicians and other stakeholders to share the latest advances in cancer science and medicine. Here, we outline some highlights of the 2024 meeting.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"360-360"},"PeriodicalIF":78.5,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881298","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}
{"title":"A MEGA RNA-editing tool","authors":"Victor Tieu","doi":"10.1038/s41568-024-00695-6","DOIUrl":"10.1038/s41568-024-00695-6","url":null,"abstract":"In this Tools of the Trade article, Victor Tieu describes the development of MEGA, a platform that exploits the RNA-targeting capability of CRISPR–Cas13d and demonstrates its use to improve the anti-tumour activity of CAR T cells.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 8","pages":"519-519"},"PeriodicalIF":72.5,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845462","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}
{"title":"Histological transformation to small-cell carcinoma","authors":"Songji Oh, Tae Min Kim","doi":"10.1038/s41568-024-00697-4","DOIUrl":"10.1038/s41568-024-00697-4","url":null,"abstract":"In this Journal Club, Oh and Kim discuss a study demonstrating the mechanisms underlying histological transformation of lung adenocarcinoma to neuroendocrine small-cell lung cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 7","pages":"447-447"},"PeriodicalIF":72.5,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140819488","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}
Xiaolong Chen, Wentao Yang, Charles W. M. Roberts, Jinghui Zhang
{"title":"Developmental origins shape the paediatric cancer genome","authors":"Xiaolong Chen, Wentao Yang, Charles W. M. Roberts, Jinghui Zhang","doi":"10.1038/s41568-024-00684-9","DOIUrl":"10.1038/s41568-024-00684-9","url":null,"abstract":"In the past two decades, technological advances have brought unprecedented insights into the paediatric cancer genome revealing characteristics distinct from those of adult cancer. Originating from developing tissues, paediatric cancers generally have low mutation burden and are driven by variants that disrupt the transcriptional activity, chromatin state, non-coding cis-regulatory regions and other biological functions. Within each tumour, there are multiple populations of cells with varying states, and the lineages of some can be tracked to their fetal origins. Genome-wide genetic screening has identified vulnerabilities associated with both the cell of origin and transcription deregulation in paediatric cancer, which have become a valuable resource for designing new therapeutic approaches including those for small molecules, immunotherapy and targeted protein degradation. In this Review, we present recent findings on these facets of paediatric cancer from a pan-cancer perspective and provide an outlook on future investigations. In this Review, Zhang and colleagues provide an overview of the molecular characteristics of paediatric cancer and highlight how these malignancies arise from developmental aberrations resulting in paediatric-specific cancer genomes that influence both the initiation and progression of cancer. Additionally, they discuss genetic vulnerabilities within these cancer genomes that present opportunities for therapeutic interventions.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"382-398"},"PeriodicalIF":78.5,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140819529","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}
{"title":"Too much of a good thing","authors":"Anna Dart","doi":"10.1038/s41568-024-00698-3","DOIUrl":"10.1038/s41568-024-00698-3","url":null,"abstract":"Dias et al. have shown that intentional further activation of oncogenic signalling rather than its inhibition represents an alternative strategy leading to colorectal cancer cell death with tumour suppressive acquired resistance.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"360-360"},"PeriodicalIF":78.5,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817818","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}
{"title":"Using the tumour microenvironment to improve therapy efficacy","authors":"Zuzana Tatarova","doi":"10.1038/s41568-024-00693-8","DOIUrl":"10.1038/s41568-024-00693-8","url":null,"abstract":"In this Tools of the Trade article, Zuzana Tatarova describes the development of MIMA, an integrated analytical platform providing the quantitative information on tumour microenvironment drug responses required for effective treatment design.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 7","pages":"444-444"},"PeriodicalIF":72.5,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648623","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}
{"title":"Investigating immune cells across time in vivo","authors":"Daniel Kirschenbaum","doi":"10.1038/s41568-024-00692-9","DOIUrl":"10.1038/s41568-024-00692-9","url":null,"abstract":"In this Tools of the Trade article, Daniel Kirschenbaum describes the development of Zman-seq and its utility for capturing dynamic changes in cellular state within single-cell RNA sequencing data.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"359-359"},"PeriodicalIF":78.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632349","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}
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