Pub Date : 2024-05-22DOI: 10.1038/s41571-024-00907-w
Maria Vittoria Dieci, Valentina Guarneri
De-escalation of treatment for HER2+ breast cancer is a priority, given the increase in cure rates owing in part to improved HER2-targeted therapies. In this regard, the neoadjuvant approach provides the ideal platform to test less-intensive treatment regimens. Here we highlight a study that demonstrated the role of the metabolic response after dual HER2 blockade as a method of selecting patients who are most likely to benefit from chemotherapy-free neoadjuvant therapy.
{"title":"Gaining ground in personalized breast cancer therapy: lesson learned from PHERGain","authors":"Maria Vittoria Dieci, Valentina Guarneri","doi":"10.1038/s41571-024-00907-w","DOIUrl":"10.1038/s41571-024-00907-w","url":null,"abstract":"De-escalation of treatment for HER2+ breast cancer is a priority, given the increase in cure rates owing in part to improved HER2-targeted therapies. In this regard, the neoadjuvant approach provides the ideal platform to test less-intensive treatment regimens. Here we highlight a study that demonstrated the role of the metabolic response after dual HER2 blockade as a method of selecting patients who are most likely to benefit from chemotherapy-free neoadjuvant therapy.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 9","pages":"643-644"},"PeriodicalIF":81.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079193","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 : 2024-05-21DOI: 10.1038/s41571-024-00906-x
Elie Rassy, Nicholas Pavlidis
The majority of patients with cancers of unknown primary have unfavourable outcomes when they receive empirical chemotherapy. The shift towards using precision medicine-based treatment strategies involves two options: tissue-agnostic or site-specific approaches. Here, we reflect on how cytology-based deep learning tools can be leveraged in these approaches.
{"title":"Predicting tumour origin with cytology-based deep learning: hype or hope?","authors":"Elie Rassy, Nicholas Pavlidis","doi":"10.1038/s41571-024-00906-x","DOIUrl":"10.1038/s41571-024-00906-x","url":null,"abstract":"The majority of patients with cancers of unknown primary have unfavourable outcomes when they receive empirical chemotherapy. The shift towards using precision medicine-based treatment strategies involves two options: tissue-agnostic or site-specific approaches. Here, we reflect on how cytology-based deep learning tools can be leveraged in these approaches.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 9","pages":"641-642"},"PeriodicalIF":81.1,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073798","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 : 2024-05-20DOI: 10.1038/s41571-024-00903-0
Jennifer N. Brudno, James N. Kochenderfer
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of several haematological malignancies and is being investigated in patients with various solid tumours. Characteristic CAR T cell-associated toxicities such as cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are now well-recognized, and improved supportive care and management with immunosuppressive agents has made CAR T cell therapy safer and more feasible than it was when the first regulatory approvals of such treatments were granted in 2017. The increasing clinical experience with these therapies has also improved recognition of previously less well-defined toxicities, including movement disorders, immune effector cell-associated haematotoxicity (ICAHT) and immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), as well as the substantial risk of infection in patients with persistent CAR T cell-induced B cell aplasia and hypogammaglobulinaemia. A more diverse selection of immunosuppressive and supportive-care pharmacotherapies is now being utilized for toxicity management, yet no universal algorithm for their application exists. As CAR T cell products targeting new antigens are developed, additional toxicities involving damage to non-malignant tissues expressing the target antigen are a potential hurdle. Continued prospective evaluation of toxicity management strategies and the design of less-toxic CAR T cell products are both crucial for ongoing success in this field. In this Review, we discuss the evolving understanding and clinical management of CAR T cell-associated toxicities. Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of various haematological malignancies but is associated with characteristic toxicities as well as less well-defined adverse effects, many of which can be severe and potentially fatal. The increasing clinical experience with CAR T cell products has resulted in better recognition and management of these toxicities using a range of pharmacotherapies, although this is an area of continued evolution and refinement. In this Review, Brudno and Kochenderfer discuss the current understanding and clinical management of CAR T cell-associated toxicities.
嵌合抗原受体（CAR）T 细胞疗法彻底改变了多种血液恶性肿瘤的治疗，目前正在对各种实体瘤患者进行研究。细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）等CAR T细胞相关毒性特征现已得到广泛认可，支持性护理和免疫抑制剂管理的改善使CAR T细胞疗法比2017年监管机构首次批准此类疗法时更加安全可行。这些疗法的临床经验不断增加，也提高了对以前不太明确的毒性的认识，包括运动障碍、免疫效应细胞相关血液毒性（ICAHT）和免疫效应细胞相关嗜血细胞淋巴细胞增多症样综合征（IEC-HS），以及持续性CAR T细胞诱导的B细胞增生和低丙种球蛋白血症患者的巨大感染风险。目前，免疫抑制和支持治疗药物疗法的选择更加多样化，用于毒性管理，但还没有通用的应用算法。随着以新抗原为靶点的 CAR T 细胞产品的开发，涉及表达靶抗原的非恶性组织损伤的额外毒性是一个潜在的障碍。继续对毒性管理策略进行前瞻性评估以及设计毒性较低的 CAR T 细胞产品，对于该领域的持续成功至关重要。在本综述中，我们将讨论对 CAR T 细胞相关毒性不断发展的理解和临床管理。
{"title":"Current understanding and management of CAR T cell-associated toxicities","authors":"Jennifer N. Brudno, James N. Kochenderfer","doi":"10.1038/s41571-024-00903-0","DOIUrl":"10.1038/s41571-024-00903-0","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of several haematological malignancies and is being investigated in patients with various solid tumours. Characteristic CAR T cell-associated toxicities such as cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are now well-recognized, and improved supportive care and management with immunosuppressive agents has made CAR T cell therapy safer and more feasible than it was when the first regulatory approvals of such treatments were granted in 2017. The increasing clinical experience with these therapies has also improved recognition of previously less well-defined toxicities, including movement disorders, immune effector cell-associated haematotoxicity (ICAHT) and immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), as well as the substantial risk of infection in patients with persistent CAR T cell-induced B cell aplasia and hypogammaglobulinaemia. A more diverse selection of immunosuppressive and supportive-care pharmacotherapies is now being utilized for toxicity management, yet no universal algorithm for their application exists. As CAR T cell products targeting new antigens are developed, additional toxicities involving damage to non-malignant tissues expressing the target antigen are a potential hurdle. Continued prospective evaluation of toxicity management strategies and the design of less-toxic CAR T cell products are both crucial for ongoing success in this field. In this Review, we discuss the evolving understanding and clinical management of CAR T cell-associated toxicities. Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of various haematological malignancies but is associated with characteristic toxicities as well as less well-defined adverse effects, many of which can be severe and potentially fatal. The increasing clinical experience with CAR T cell products has resulted in better recognition and management of these toxicities using a range of pharmacotherapies, although this is an area of continued evolution and refinement. In this Review, Brudno and Kochenderfer discuss the current understanding and clinical management of CAR T cell-associated toxicities.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 7","pages":"501-521"},"PeriodicalIF":81.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071276","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 : 2024-05-17DOI: 10.1038/s41571-024-00904-z
Talía Malagón, Eduardo L. Franco, Romina Tejada, Salvatore Vaccarella
Cervical cancer is the first cancer deemed amenable to elimination through prevention, and thus lessons from the epidemiology and prevention of this cancer type can provide information on strategies to manage other cancers. Infection with the human papillomavirus (HPV) causes virtually all cervical cancers, and an important proportion of oropharyngeal, anal and genital cancers. Whereas 20th century prevention efforts were dominated by cytology-based screening, the present and future of HPV-associated cancer prevention relies mostly on HPV vaccination and molecular screening tests. In this Review, we provide an overview of the epidemiology of HPV-associated cancers, their disease burden, how past and contemporary preventive interventions have shaped their incidence and mortality, and the potential for elimination. We particularly focus on the cofactors that could have the greatest effect on prevention efforts, such as parity and human immunodeficiency virus infection, as well as on social determinants of health. Given that the incidence of and mortality from HPV-associated cancers remain strongly associated with the socioeconomic status of individuals and the human development index of countries, elimination efforts are unlikely to succeed unless prevention efforts focus on health equity, with a commitment to both primary and secondary prevention. Lessons from the prevention of cervical cancer, the first cancer type deemed amenable to elimination, can provide information on strategies to manage other cancers. Infection with human papillomavirus (HPV) causes virtually all cervical cancers and an important proportion of other cancer types. The authors of this Review discuss the epidemiology of HPV-associated cancers and the potential for their elimination, focusing on the cofactors that could have the greatest effect on prevention efforts and health equity.
{"title":"Epidemiology of HPV-associated cancers past, present and future: towards prevention and elimination","authors":"Talía Malagón, Eduardo L. Franco, Romina Tejada, Salvatore Vaccarella","doi":"10.1038/s41571-024-00904-z","DOIUrl":"10.1038/s41571-024-00904-z","url":null,"abstract":"Cervical cancer is the first cancer deemed amenable to elimination through prevention, and thus lessons from the epidemiology and prevention of this cancer type can provide information on strategies to manage other cancers. Infection with the human papillomavirus (HPV) causes virtually all cervical cancers, and an important proportion of oropharyngeal, anal and genital cancers. Whereas 20th century prevention efforts were dominated by cytology-based screening, the present and future of HPV-associated cancer prevention relies mostly on HPV vaccination and molecular screening tests. In this Review, we provide an overview of the epidemiology of HPV-associated cancers, their disease burden, how past and contemporary preventive interventions have shaped their incidence and mortality, and the potential for elimination. We particularly focus on the cofactors that could have the greatest effect on prevention efforts, such as parity and human immunodeficiency virus infection, as well as on social determinants of health. Given that the incidence of and mortality from HPV-associated cancers remain strongly associated with the socioeconomic status of individuals and the human development index of countries, elimination efforts are unlikely to succeed unless prevention efforts focus on health equity, with a commitment to both primary and secondary prevention. Lessons from the prevention of cervical cancer, the first cancer type deemed amenable to elimination, can provide information on strategies to manage other cancers. Infection with human papillomavirus (HPV) causes virtually all cervical cancers and an important proportion of other cancer types. The authors of this Review discuss the epidemiology of HPV-associated cancers and the potential for their elimination, focusing on the cofactors that could have the greatest effect on prevention efforts and health equity.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 7","pages":"522-538"},"PeriodicalIF":81.1,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953505","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 : 2024-05-17DOI: 10.1038/s41571-024-00902-1
Elias J. Sayour, David Boczkowski, Duane A. Mitchell, Smita K. Nair
mRNA vaccines have been revolutionary in terms of their rapid development and prevention of SARS-CoV-2 infections during the COVID-19 pandemic, and this technology has considerable potential for application to the treatment of cancer. Compared with traditional cancer vaccines based on proteins or peptides, mRNA vaccines reconcile the needs for both personalization and commercialization in a manner that is unique to each patient but not beholden to their HLA haplotype. A further advantage of mRNA vaccines is the availability of engineering strategies to improve their stability while retaining immunogenicity, enabling the induction of complementary innate and adaptive immune responses. Thus far, no mRNA-based cancer vaccines have received regulatory approval, although several phase I–II trials have yielded promising results, including in historically poorly immunogenic tumours. Furthermore, many early phase trials testing a wide range of vaccine designs are currently ongoing. In this Review, we describe the advantages of cancer mRNA vaccines and advances in clinical trials using both cell-based and nanoparticle-based delivery methods, with discussions of future combinations and iterations that might optimize the activity of these agents. Following their successful implementation in the COVID-19 pandemic, the technology behind mRNA vaccines is now being applied to cancer. In this Review, the authors described the several decades of development of mRNA vaccines for patients with cancer, including initial developments in this area involving cell-based vaccines as well as more recent developments with nanoparticle-encapsulated vaccines, which are beginning to show promising clinical activity.
{"title":"Cancer mRNA vaccines: clinical advances and future opportunities","authors":"Elias J. Sayour, David Boczkowski, Duane A. Mitchell, Smita K. Nair","doi":"10.1038/s41571-024-00902-1","DOIUrl":"10.1038/s41571-024-00902-1","url":null,"abstract":"mRNA vaccines have been revolutionary in terms of their rapid development and prevention of SARS-CoV-2 infections during the COVID-19 pandemic, and this technology has considerable potential for application to the treatment of cancer. Compared with traditional cancer vaccines based on proteins or peptides, mRNA vaccines reconcile the needs for both personalization and commercialization in a manner that is unique to each patient but not beholden to their HLA haplotype. A further advantage of mRNA vaccines is the availability of engineering strategies to improve their stability while retaining immunogenicity, enabling the induction of complementary innate and adaptive immune responses. Thus far, no mRNA-based cancer vaccines have received regulatory approval, although several phase I–II trials have yielded promising results, including in historically poorly immunogenic tumours. Furthermore, many early phase trials testing a wide range of vaccine designs are currently ongoing. In this Review, we describe the advantages of cancer mRNA vaccines and advances in clinical trials using both cell-based and nanoparticle-based delivery methods, with discussions of future combinations and iterations that might optimize the activity of these agents. Following their successful implementation in the COVID-19 pandemic, the technology behind mRNA vaccines is now being applied to cancer. In this Review, the authors described the several decades of development of mRNA vaccines for patients with cancer, including initial developments in this area involving cell-based vaccines as well as more recent developments with nanoparticle-encapsulated vaccines, which are beginning to show promising clinical activity.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 7","pages":"489-500"},"PeriodicalIF":81.1,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954207","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 : 2024-05-07DOI: 10.1038/s41571-024-00898-8
Vinay Prasad
The question of whether chimeric antigen receptor (CAR) T cell therapies should be used in earlier lines (after 1–2 prior lines of therapy) in patients with relapsed and/or refractory multiple myeloma remains unanswered. Herein, I argue that the use of surrogate end points that lack a robust correlation with overall survival, as well as suboptimal control arms and use of post-progression therapies, limit the ability to make definitive conclusions on the basis of the available data.
{"title":"CAR T cells in multiple myeloma: lessons learned","authors":"Vinay Prasad","doi":"10.1038/s41571-024-00898-8","DOIUrl":"10.1038/s41571-024-00898-8","url":null,"abstract":"The question of whether chimeric antigen receptor (CAR) T cell therapies should be used in earlier lines (after 1–2 prior lines of therapy) in patients with relapsed and/or refractory multiple myeloma remains unanswered. Herein, I argue that the use of surrogate end points that lack a robust correlation with overall survival, as well as suboptimal control arms and use of post-progression therapies, limit the ability to make definitive conclusions on the basis of the available data.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 8","pages":"563-564"},"PeriodicalIF":81.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845414","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 : 2024-05-01DOI: 10.1038/s41571-024-00892-0
Zeyu Zhang, Yang Du, Xiaojing Shi, Kun Wang, Qiaojun Qu, Qian Liang, Xiaopeng Ma, Kunshan He, Chongwei Chi, Jianqiang Tang, Bo Liu, Jiafu Ji, Jun Wang, Jiahong Dong, Zhenhua Hu, Jie Tian
Novel strategies utilizing light in the second near-infrared region (NIR-II; 900–1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities. Expansion of the utilizable spectrum of light from the visible region to the near-infrared (NIR) window has greatly facilitated the clinical application of optical technologies for cancer imaging and phototherapy. However, use of light in the first NIR region (NIR-I) has important limitations, some of which might be overcome with emerging technologies utilizing NIR-II light. In this Review, the authors describe the current clinical experience with NIR-II-based cancer imaging and phototherapy, and discuss emerging NIR-II-based approaches that might further enhance patient outcomes. They also highlight challenges that will need to be addressed to translate NIR-II-based modalities from bench to bedside.
{"title":"NIR-II light in clinical oncology: opportunities and challenges","authors":"Zeyu Zhang, Yang Du, Xiaojing Shi, Kun Wang, Qiaojun Qu, Qian Liang, Xiaopeng Ma, Kunshan He, Chongwei Chi, Jianqiang Tang, Bo Liu, Jiafu Ji, Jun Wang, Jiahong Dong, Zhenhua Hu, Jie Tian","doi":"10.1038/s41571-024-00892-0","DOIUrl":"10.1038/s41571-024-00892-0","url":null,"abstract":"Novel strategies utilizing light in the second near-infrared region (NIR-II; 900–1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities. Expansion of the utilizable spectrum of light from the visible region to the near-infrared (NIR) window has greatly facilitated the clinical application of optical technologies for cancer imaging and phototherapy. However, use of light in the first NIR region (NIR-I) has important limitations, some of which might be overcome with emerging technologies utilizing NIR-II light. In this Review, the authors describe the current clinical experience with NIR-II-based cancer imaging and phototherapy, and discuss emerging NIR-II-based approaches that might further enhance patient outcomes. They also highlight challenges that will need to be addressed to translate NIR-II-based modalities from bench to bedside.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 6","pages":"449-467"},"PeriodicalIF":78.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817789","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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