Nature Reviews Clinical Oncology最新文献

{"title":"The transformative role of SBRT in the management of spinal metastases","authors":"K. Liang Zeng, Pejman Jabehdar Maralani, Michael Hardisty, Hanbo Chen, Jay Detsky, Deepak Dinakaran, Hany Soliman, Chia-Lin Tseng, Jeremie Larouche, Jetan Badhiwala, Elizabeth David, Katarzyna J. Jerzak, Amit Singnurkar, Chris Heyn, Cari Whyne, Mark Ruschin, Arjun Sahgal","doi":"10.1038/s41571-026-01152-z","DOIUrl":"10.1038/s41571-026-01152-z","url":null,"abstract":"Spinal metastases can cause disabling pain and neurological deterioration and have historically been treated with palliative intent and conventional external beam radiotherapy (cEBRT). A fundamental shift away from the short-term palliative goals associated with cEBRT has taken place over the past two decades following the availability of stereotactic body radiotherapy (SBRT). This technique has enabled durable pain relief and local control owing to the ability to precisely deliver high radiation doses across typically up to five fractions, with level 1 evidence supporting superior complete pain response rates and local tumour control compared with cEBRT. The development of spinal SBRT has also resulted in greater multidisciplinary collaboration, with neuroradiologists, spinal surgeons, interventional radiologists, biomechanical engineers, medical physicists, medical oncologists and radiation oncologists working together with the common goal of improving our understanding of the pathophysiology and treatment of spinal metastases. As a result, substantial gains have been realized in refining patient selection and treatment sequencing, and particularly the development of less-invasive surgical procedures. In this Review, we summarize the development and role of SBRT in the management of spinal metastases. Spinal metastases are associated with debilitating pain and neurological deterioration as well as a poor prognosis and have historically been managed with a palliative intent. Now, following the emergence of stereotactic body radiotherapy (SBRT), more effective pain control as well as control of the metastatic lesions is becoming feasible. In this Review, the authors describe the development and role of SBRT in the management of spinal metastases.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 8","pages":"582-602"},"PeriodicalIF":94.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840682","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":"Synergistic integration of regional and systemic therapies in uveal melanoma","authors":"Shaheer A. Khan, Richard D. Carvajal","doi":"10.1038/s41571-026-01155-w","DOIUrl":"10.1038/s41571-026-01155-w","url":null,"abstract":"Treatments for metastatic uveal melanoma utilize various liver-directed strategies, yet optimal integration with systemic therapy is unclear. Here we examine recent evidence indicating that combining percutaneous hepatic perfusion with immune-checkpoint inhibitors might improve patient outcomes, compare it with data from other trials and highlight key questions around patient selection, sequencing and mechanisms that will shape future strategies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 7","pages":"477-478"},"PeriodicalIF":94.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776944","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":"The clinical landscape of HIF2α inhibitors in oncology","authors":"Eddy Saad, Marc Machaalani, David F. McDermott, Toni K. Choueiri","doi":"10.1038/s41571-026-01145-y","DOIUrl":"10.1038/s41571-026-01145-y","url":null,"abstract":"Hypoxia-inducible factor 2α (HIF2α; also known as endothelial PAS domain-containing protein 1) had long been considered an undruggable transcription factor until the discovery of an allosteric pocket within its PAS-B domain enabled the development of selective small-molecule antagonists. Belzutifan, the first-in-class HIF2α inhibitor, has since demonstrated substantial efficacy in patients with von Hippel–Lindau (VHL) disease-associated tumours, sporadic clear-cell renal cell carcinoma (ccRCC), and pheochromocytoma or paraganglioma, thereby validating HIF2α as a therapeutic target in patients with cancer. In this Review, we summarize the biology of the VHL–HIF signalling pathway, the structural basis for HIF2α druggability and the clinical milestones leading to the multiple regulatory approvals of belzutifan. We also highlight emerging data on other small-molecule inhibitors, RNA interference approaches and indirect modulators that have the potential to expand the scope of HIF pathway suppression. Combination strategies offer opportunities to enhance efficacy and overcome resistance; however, key challenges remain, including the identification of predictive biomarkers, mechanisms of primary and acquired resistance, and optimal management approaches for on-target toxicities such as anaemia and hypoxia. Finally, we discuss the increasing potential of HIF2α inhibition beyond kidney cancer, including its role in hypoxia-adapted malignancies, and outline priorities for future translational and clinical research. Long considered undruggable, hypoxia-inducible factor 2α (HIF2α) has now been validated as a therapeutic target in several cancers. This Review discusses the structural basis for HIF2α druggability, the clinical results to date and key challenges, including toxicities and the need for predictive biomarkers, as well as emerging targeting modalities and combination strategies that might enhance efficacy, overcome resistance and broaden indications for HIF2 inhibition.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 7","pages":"501-519"},"PeriodicalIF":94.6,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754600","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":"Emerging trends in the global burden of colorectal cancer","authors":"David J. Lee, Aparna Parikh, Bhawna Sirohi, Yin Cao, Andrew T. Chan","doi":"10.1038/s41571-026-01149-8","DOIUrl":"10.1038/s41571-026-01149-8","url":null,"abstract":"Globally, colorectal cancer (CRC) is the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths, although these epidemiological patterns show substantial geographical variation. In this Review, we discuss the emerging global patterns of CRC incidence, which historically has been the highest among Western, high-income countries but is now increasing globally beyond these regions. This rise has mainly been driven by early-onset CRC — that is, cancers diagnosed in individuals aged <50 years. A birth cohort effect beginning with individuals born in the 1960s indicates that factors beyond genetic susceptibility or changes in screening practice underlie this increase. A changing landscape of established and emerging risk factors occurring worldwide has been proposed to underlie these epidemiological trends in CRC. Hypothesized risk factors include dietary and lifestyle aspects, shifts in the gut microbiota and the rise in environmental contaminants associated with the rapid urbanization occurring globally. Substantial advances in the characterization of genomic and epigenomic profiles of CRCs as well as their gut microbiomes not only hold potential for providing insight on the aetiology of this disease but could also be leveraged for early detection and interception strategies. The under-representation of non-Western populations in these studies, however, greatly limits progress and, if not addressed, could widen the existing gaps in global CRC prevention and control. The incidence of colorectal cancer (CRC) has historically been the highest among Western, high-income countries but is now increasing globally beyond these regions. Early-onset CRC (diagnosed before the age of 50 years) has been the main driver of this rise, and risk factors including dietary and lifestyle aspects, the gut microbiota and environmental contaminants have been proposed to underlie these epidemiological trends. The authors of this Review discuss the available evidence on these risk factors, highlighting how the under-representation of non-Western populations in these studies is limiting progress.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 8","pages":"569-581"},"PeriodicalIF":94.6,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754598","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":"Did ATOMIC really improve on the standard of care for mismatch repair-deficient colon cancer?","authors":"Javier-David Benitez-Fuentes, Deme Karikios, Bishal Gyawali","doi":"10.1038/s41571-026-01154-x","DOIUrl":"10.1038/s41571-026-01154-x","url":null,"abstract":"The ATOMIC trial has been widely celebrated as providing a positive result. However, when viewed with a lens of critical appraisal that considers issues related to overtreatment, treatment de-escalation, surrogacy, post-trial access to treatment and contributions of component, we argue that ATOMIC should not change clinical practice but rather form the basis for future trials that test de-escalation strategies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 7","pages":"471-472"},"PeriodicalIF":94.6,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735438","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":"Systemic induction therapy and the expanding frontier of bladder preservation in MIBC","authors":"Laura S. Mertens, Ashish M. Kamat","doi":"10.1038/s41571-026-01153-y","DOIUrl":"10.1038/s41571-026-01153-y","url":null,"abstract":"Two recent phase II trials, INDIBLADE and SURE-02, challenge the long-standing paradigm of mandatory radical local therapy for muscle-invasive bladder cancer (MIBC). As increasingly potent systemic induction treatment strategies emerge, a key question arises: can induction therapy response guide omission of radical surgery and radiotherapy to enable preservation of an intact, functioning bladder in selected patients?","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 6","pages":"399-400"},"PeriodicalIF":82.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733315","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":"Time as an unmeasured ‘dose’ in oncology: introducing time budgeting as a design principle for cancer care","authors":"Sunil Shrestha, Pratik Khanal, Enrique Soto-Perez-de-Celis","doi":"10.1038/s41571-026-01151-0","DOIUrl":"10.1038/s41571-026-01151-0","url":null,"abstract":"The burden of cancer therapy on patients’ time is often overlooked. Building on the ‘time toxicity’ literature, we introduce the concept of time budgeting, viewing patients’ time as a limited, measurable resource that can be managed through treatment selection, pathway design and trial protocols. We discuss the rationale, measurement challenges and implementation requirements to operationalize time budgeting in cancer care.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 6","pages":"396-397"},"PeriodicalIF":82.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731607","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":"OS benefit with first-line datopotamab deruxtecan in advanced-stage TNBC","authors":"Diana Romero","doi":"10.1038/s41571-026-01150-1","DOIUrl":"10.1038/s41571-026-01150-1","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 6","pages":"398-398"},"PeriodicalIF":82.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684706","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":"Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders","authors":"Alaa Ali, Metin Ozdemirli, Mark P. Hamilton, Michael D. Jain","doi":"10.1038/s41571-026-01147-w","DOIUrl":"10.1038/s41571-026-01147-w","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy is now widely used for the treatment of various haematological malignancies, with emerging applications in solid tumours and autoimmune diseases. Alongside its demonstrated clinical activity, this therapeutic modality has a toxicity profile that differs from those associated with traditional cytotoxic therapies, other immunotherapies, and even other cell therapy approaches such as allogeneic haematopoietic stem cell transplantation. One increasingly recognized yet poorly understood complication is the development of post-CAR T cell therapy lymphoproliferative and lymphomatous disorders, which have a clinical and biological spectrum that remains incompletely characterized. These rare events include both CAR-transgene-positive and transgene-negative lymphomas with variable and sometimes overlapping clinical features. Causal attribution is difficult, given that these proliferations often emerge in the context of clonal haematopoiesis, inflammatory or infectious triggers, immune suppression and/or viral reactivation. In this Review, we synthesize the growing body of evidence on post-CAR T cell therapy lymphoproliferative disorders, drawing on the limited but increasing number of well-characterized cases. We outline the spectrum of lymphoproliferations described so far, highlight recurrent pathological and molecular features, and discuss factors that might promote clonal expansion or transformation, including pre-existing clonal haematopoiesis, dysregulated signalling pathways, inflammatory stimuli and, rarely, CAR-transgene vector integration. A clearer framework for these disorders might improve early recognition, guide diagnostic evaluation, support treatment decision-making, facilitate classification and consensus-building efforts, and inform future mechanistic studies and pharmacovigilance efforts. Rare lymphoproliferative and lymphomatous disorders occurring after chimeric antigen receptor (CAR) T cell therapy are garnering increased attention but remain incompletely characterized, complicating early recognition and management. This Review describes the spectrum of post-CAR T cell therapy lymphoproliferations reported so far, highlighting recurrent pathological and molecular features as well as factors implicated in promoting clonal expansion and/or malignant transformation, which might provide a framework to improve the diagnosis and management of these disorders.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 7","pages":"520-538"},"PeriodicalIF":94.6,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684704","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 2026 update on myelodysplastic neoplasms: current state, challenges and future directions","authors":"Jan Philipp Bewersdorf, Alain Mina, Maximilian Stahl, Amer M. Zeidan","doi":"10.1038/s41571-026-01141-2","DOIUrl":"10.1038/s41571-026-01141-2","url":null,"abstract":"Myelodysplastic neoplasms, also known as myelodysplastic syndromes (MDS), are a heterogeneous group of myeloid malignancies characterized by ineffective haematopoiesis, cytopenias and a variably increased risk of progression to acute myeloid leukaemia. MDS primarily affect older adults with a median age at diagnosis of 76 years among patients in the USA. Despite major advances in our understanding of the genetic landscape and pathophysiology of MDS over the past 20 years, few disease-modifying therapies have been approved. Allogeneic haematopoietic stem cell transplantation remains the only potentially curative option. This slow therapeutic progress likely reflects the complex and widely heterogeneous pathophysiology of MDS, including a multifaceted interplay of somatic and germline mutations, a dysfunctional immune system, and an inflamed bone marrow microenvironment. Despite improvements in diagnostic tools, classification systems and prognostic models, these changes have introduced challenges for clinical trial design and epidemiological reporting. In this Review, we provide an update on the epidemiology, diagnosis, risk stratification, classification and expanding therapeutic armamentarium for the management of MDS. We also provide an overview of the current challenges to further progress and discuss future directions of research, which will hopefully lead to the development and approval of novel and effective therapies. Myelodysplastic neoplasms (MDS) comprise a heterogeneous group of malignancies that can lead to ineffective haematopoiesis, cytopenias and, potentially, progression to acute myeloid leukaemia. In this Review, the authors describe the epidemiology of MDS, which appears to be rising, as well as advances in diagnosis, risk stratification and clinical management.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 7","pages":"481-500"},"PeriodicalIF":94.6,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41571-026-01141-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680608","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}