Pub Date : 2024-10-01DOI: 10.1038/s41571-024-00950-7
The November 2024 issue of Nature Reviews Clinical Oncology marks the 20th anniversary of the journal. Here, we reflect on the role of the journal during a time in which the clinical oncology community has witnessed many important changes.
{"title":"Reflecting on the past 20 years in oncology","authors":"","doi":"10.1038/s41571-024-00950-7","DOIUrl":"10.1038/s41571-024-00950-7","url":null,"abstract":"The November 2024 issue of Nature Reviews Clinical Oncology marks the 20th anniversary of the journal. Here, we reflect on the role of the journal during a time in which the clinical oncology community has witnessed many important changes.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"763-763"},"PeriodicalIF":81.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-024-00950-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360347","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 : 2024-10-01DOI: 10.1038/s41571-024-00945-4
Susana Banerjee, Christopher M. Booth, Eduardo Bruera, Markus W. Büchler, Alexander Drilon, Terry J. Fry, Irene M. Ghobrial, Luca Gianni, Rakesh K. Jain, Guido Kroemer, Josep M. Llovet, Georgina V. Long, Klaus Pantel, Kathy Pritchard-Jones, Howard I. Scher, Josep Tabernero, Ralph R. Weichselbaum, Michael Weller, Yi-Long Wu
Since the publication of the first issue of Nature Reviews Clinical Oncology, we have witnessed advances in multiple research areas that have culminated in improved outcomes for many cancer types, although substantial unmet needs remain for a majority of patients worldwide. Here, we have asked experts in several key specialities to reflect on the progress from the past 20 years and propose the next steps to enable further advances. Although we are aware that this Viewpoint cannot provide full coverage of the vast field that is clinical oncology, we hope that these messages inspire a diverse range of readers.
{"title":"Two decades of advances in clinical oncology — lessons learned and future directions","authors":"Susana Banerjee, Christopher M. Booth, Eduardo Bruera, Markus W. Büchler, Alexander Drilon, Terry J. Fry, Irene M. Ghobrial, Luca Gianni, Rakesh K. Jain, Guido Kroemer, Josep M. Llovet, Georgina V. Long, Klaus Pantel, Kathy Pritchard-Jones, Howard I. Scher, Josep Tabernero, Ralph R. Weichselbaum, Michael Weller, Yi-Long Wu","doi":"10.1038/s41571-024-00945-4","DOIUrl":"10.1038/s41571-024-00945-4","url":null,"abstract":"Since the publication of the first issue of Nature Reviews Clinical Oncology, we have witnessed advances in multiple research areas that have culminated in improved outcomes for many cancer types, although substantial unmet needs remain for a majority of patients worldwide. Here, we have asked experts in several key specialities to reflect on the progress from the past 20 years and propose the next steps to enable further advances. Although we are aware that this Viewpoint cannot provide full coverage of the vast field that is clinical oncology, we hope that these messages inspire a diverse range of readers.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"771-780"},"PeriodicalIF":81.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-024-00945-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360348","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 : 2024-09-26DOI: 10.1038/s41571-024-00946-3
Claudia A. J. van Winkel, Frank R. Pierik, Adrienne H. Brouwers, Derk Jan A. de Groot, Elisabeth G. E. de Vries, Marjolijn N. Lub-de Hooge
Multispecific antibodies are engineered antibody derivatives that can bind to two or more distinct epitopes or antigens. Unlike mixtures of monospecific antibodies, the binding properties of multispecific antibodies enable two specific molecules to be physically linked, a characteristic with important applications in cancer therapy. The field of multispecific antibodies is highly dynamic and expanding rapidly; to date, 15 multispecific antibodies have been approved for clinical use, of which 11 were approved for oncological indications, and more than 100 new antibodies are currently in clinical development. Nevertheless, substantial challenges limit the applications of multispecific antibodies in cancer therapy, particularly inefficient targeting of solid tumours and substantial adverse effects. Both PET and single photon emission CT imaging can reveal the biodistribution and complex pharmacology of radiolabelled multispecific antibodies. This Review summarizes the insights obtained from preclinical and clinical molecular imaging studies of multispecific antibodies, focusing on their structural properties, such as molecular weight, shape, target specificity, affinity and avidity. The opportunities associated with use of molecular imaging studies to support the clinical development of multispecific antibody therapies are also highlighted. Multispecific antibody constructs that bind several distinct targets can connect cells and/or simultaneously target multiple molecules. Here, Lub-de Hooge et al. discuss the varied contributions of molecular imaging to multispecific antibody design, drug development and optimization, including evaluations of antibody biodistribution and pharmacological complexity.
{"title":"Molecular imaging supports the development of multispecific cancer antibodies","authors":"Claudia A. J. van Winkel, Frank R. Pierik, Adrienne H. Brouwers, Derk Jan A. de Groot, Elisabeth G. E. de Vries, Marjolijn N. Lub-de Hooge","doi":"10.1038/s41571-024-00946-3","DOIUrl":"10.1038/s41571-024-00946-3","url":null,"abstract":"Multispecific antibodies are engineered antibody derivatives that can bind to two or more distinct epitopes or antigens. Unlike mixtures of monospecific antibodies, the binding properties of multispecific antibodies enable two specific molecules to be physically linked, a characteristic with important applications in cancer therapy. The field of multispecific antibodies is highly dynamic and expanding rapidly; to date, 15 multispecific antibodies have been approved for clinical use, of which 11 were approved for oncological indications, and more than 100 new antibodies are currently in clinical development. Nevertheless, substantial challenges limit the applications of multispecific antibodies in cancer therapy, particularly inefficient targeting of solid tumours and substantial adverse effects. Both PET and single photon emission CT imaging can reveal the biodistribution and complex pharmacology of radiolabelled multispecific antibodies. This Review summarizes the insights obtained from preclinical and clinical molecular imaging studies of multispecific antibodies, focusing on their structural properties, such as molecular weight, shape, target specificity, affinity and avidity. The opportunities associated with use of molecular imaging studies to support the clinical development of multispecific antibody therapies are also highlighted. Multispecific antibody constructs that bind several distinct targets can connect cells and/or simultaneously target multiple molecules. Here, Lub-de Hooge et al. discuss the varied contributions of molecular imaging to multispecific antibody design, drug development and optimization, including evaluations of antibody biodistribution and pharmacological complexity.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"852-866"},"PeriodicalIF":81.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321319","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 : 2024-09-24DOI: 10.1038/s41571-024-00949-0
David Killock
{"title":"CABINET presents cabozantinib as a new treatment option for NETs","authors":"David Killock","doi":"10.1038/s41571-024-00949-0","DOIUrl":"10.1038/s41571-024-00949-0","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"766-766"},"PeriodicalIF":81.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313846","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 : 2024-09-24DOI: 10.1038/s41571-024-00943-6
Christopher J. M. Williams, Allyson M. Peddle, Pashtoon M. Kasi, Jenny F. Seligmann, Campbell S. Roxburgh, Gary W. Middleton, Sabine Tejpar
Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer. By contrast, metastatic CRCs with proficient DNA mismatch repair (pMMR) are generally resistant to ICIs, although a proportion of locally advanced pMMR tumours seem to have a high degree of sensitivity to ICIs. In this Review, we describe the current and emerging clinical evidence supporting the use of neoadjuvant ICIs in patients with dMMR and pMMR CRC, and the potential advantages (based on a biological rationale) of such an approach. We discuss how neoadjuvant ‘window-of-opportunity’ trials are being leveraged to progress biomarker discovery and we provide an overview of potential predictive biomarkers of response to ICIs, exploring the challenges faced when evaluating such biomarkers in biopsy-derived samples. Lastly, we describe how these discoveries might be used to drive a rational approach to trialling novel immunotherapeutic strategies in patients with pMMR CRC, with the ultimate aim of disease eradication and the generation of long-term immunosurveillance. Locally advanced colorectal cancers (CRCs) with DNA mismatch repair deficiency have sensitivity to immune-checkpoint inhibitors, and evidence suggests that this is also the case for a proportion of proficient DNA mismatch repair CRCs. The authors of this Review describe the emerging clinical evidence supporting the use of neoadjuvant immune-checkpoint inhibitors in patients with CRC and discuss how clinical research (including on biomarkers) can be used to improve clinical outcomes in this setting.
{"title":"Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response","authors":"Christopher J. M. Williams, Allyson M. Peddle, Pashtoon M. Kasi, Jenny F. Seligmann, Campbell S. Roxburgh, Gary W. Middleton, Sabine Tejpar","doi":"10.1038/s41571-024-00943-6","DOIUrl":"10.1038/s41571-024-00943-6","url":null,"abstract":"Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer. By contrast, metastatic CRCs with proficient DNA mismatch repair (pMMR) are generally resistant to ICIs, although a proportion of locally advanced pMMR tumours seem to have a high degree of sensitivity to ICIs. In this Review, we describe the current and emerging clinical evidence supporting the use of neoadjuvant ICIs in patients with dMMR and pMMR CRC, and the potential advantages (based on a biological rationale) of such an approach. We discuss how neoadjuvant ‘window-of-opportunity’ trials are being leveraged to progress biomarker discovery and we provide an overview of potential predictive biomarkers of response to ICIs, exploring the challenges faced when evaluating such biomarkers in biopsy-derived samples. Lastly, we describe how these discoveries might be used to drive a rational approach to trialling novel immunotherapeutic strategies in patients with pMMR CRC, with the ultimate aim of disease eradication and the generation of long-term immunosurveillance. Locally advanced colorectal cancers (CRCs) with DNA mismatch repair deficiency have sensitivity to immune-checkpoint inhibitors, and evidence suggests that this is also the case for a proportion of proficient DNA mismatch repair CRCs. The authors of this Review describe the emerging clinical evidence supporting the use of neoadjuvant immune-checkpoint inhibitors in patients with CRC and discuss how clinical research (including on biomarkers) can be used to improve clinical outcomes in this setting.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"839-851"},"PeriodicalIF":81.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-024-00943-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313847","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 : 2024-09-19DOI: 10.1038/s41571-024-00947-2
Peter Sidaway
{"title":"A new standard of care for leiomyosarcoma","authors":"Peter Sidaway","doi":"10.1038/s41571-024-00947-2","DOIUrl":"10.1038/s41571-024-00947-2","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"766-766"},"PeriodicalIF":81.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245344","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 : 2024-09-13DOI: 10.1038/s41571-024-00939-2
Adrienne G. Waks, Olga Martínez-Sáez, Paolo Tarantino, Fara Braso-Maristany, Tomás Pascual, Javier Cortés, Sara M. Tolaney, Aleix Prat
HER2-targeted therapies for patients with HER2+ breast cancer are rapidly evolving, offering a range of more complex and personalized treatment options. Currently, an array of anti-HER2 monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates are administered, sometimes alongside chemotherapy or endocrine therapy, both in curative and palliative contexts. However, the heterogeneous nature of HER2+ breast cancer demands a deeper understanding of disease biology and its role in responsiveness to novel HER2-targeted agents, as well as non-HER2-targeted therapies, in order to optimize patient outcomes. In this Review, we revisit the mechanisms of action of HER2-targeted agents, examine the evidence supporting the use of dual HER2 blockade in patients with HER2-amplified tumours, and explore the role of biomarkers in guiding future treatment strategies. We also discuss potential implications for the future treatment of patients with HER2+ breast cancer. Patients with HER2+ breast cancer often respond to trastuzumab, although acquired resistance is common and can involve a range of mechanisms. reflecting the highly heterogeneous biology of this breast cancer subtype. In this Review, the authors describe the role of dual HER2 blockade, involving the co-administration of two HER2-targeted therapies (including monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates) in patients with HER2+ breast cancer.
{"title":"Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance","authors":"Adrienne G. Waks, Olga Martínez-Sáez, Paolo Tarantino, Fara Braso-Maristany, Tomás Pascual, Javier Cortés, Sara M. Tolaney, Aleix Prat","doi":"10.1038/s41571-024-00939-2","DOIUrl":"10.1038/s41571-024-00939-2","url":null,"abstract":"HER2-targeted therapies for patients with HER2+ breast cancer are rapidly evolving, offering a range of more complex and personalized treatment options. Currently, an array of anti-HER2 monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates are administered, sometimes alongside chemotherapy or endocrine therapy, both in curative and palliative contexts. However, the heterogeneous nature of HER2+ breast cancer demands a deeper understanding of disease biology and its role in responsiveness to novel HER2-targeted agents, as well as non-HER2-targeted therapies, in order to optimize patient outcomes. In this Review, we revisit the mechanisms of action of HER2-targeted agents, examine the evidence supporting the use of dual HER2 blockade in patients with HER2-amplified tumours, and explore the role of biomarkers in guiding future treatment strategies. We also discuss potential implications for the future treatment of patients with HER2+ breast cancer. Patients with HER2+ breast cancer often respond to trastuzumab, although acquired resistance is common and can involve a range of mechanisms. reflecting the highly heterogeneous biology of this breast cancer subtype. In this Review, the authors describe the role of dual HER2 blockade, involving the co-administration of two HER2-targeted therapies (including monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates) in patients with HER2+ breast cancer.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"818-832"},"PeriodicalIF":81.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174961","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 : 2024-09-12DOI: 10.1038/s41571-024-00944-5
Stanislav Lazarev, Kunal K. Sindhu
Despite recent FDA approval, the clinical utility of vorasidenib in the treatment of IDH-mutant low-grade gliomas remains unclear. Herein, we critique the pivotal trial of vorasidenib, and highlight the questionable choice of control intervention and end points, ethical concerns, as well as the uncertain efficacy observed, and argue that the approval might be premature given the high cost of this drug and lack of clear benefit over standard treatments.
{"title":"Vorasidenib: a new hope or a false promise for patients with low-grade glioma?","authors":"Stanislav Lazarev, Kunal K. Sindhu","doi":"10.1038/s41571-024-00944-5","DOIUrl":"10.1038/s41571-024-00944-5","url":null,"abstract":"Despite recent FDA approval, the clinical utility of vorasidenib in the treatment of IDH-mutant low-grade gliomas remains unclear. Herein, we critique the pivotal trial of vorasidenib, and highlight the questionable choice of control intervention and end points, ethical concerns, as well as the uncertain efficacy observed, and argue that the approval might be premature given the high cost of this drug and lack of clear benefit over standard treatments.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"835-836"},"PeriodicalIF":81.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170751","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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