Nature Reviews Clinical Oncology最新文献

{"title":"Precision oncology needs precision trial design: lessons from FGFR2-rearranged cholangiocarcinoma","authors":"Fen Saj, Lipika Goyal","doi":"10.1038/s41571-026-01194-3","DOIUrl":"10.1038/s41571-026-01194-3","url":null,"abstract":"The phase III FIGHT-302 trial demonstrated that the FGFR inhibitor pemigatinib improves progression-free survival and response rates versus first-line chemotherapy in patients with advanced-stage FGFR2-rearranged cholangiocarcinoma. However, the trial accrued slowly and closed early after chemoimmunotherapy became the new standard of care. FIGHT-302, alongside two similarly terminated trials, highlights the need for innovative trial designs and flexible regulatory frameworks to evaluate therapies in rare, biomarker-defined populations.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 11","pages":"829-830"},"PeriodicalIF":94.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727865","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":"How positive was PROTEUS? Reconsidering success when most patients never reach no evidence of disease","authors":"Daniel E. Spratt","doi":"10.1038/s41571-026-01193-4","DOIUrl":"10.1038/s41571-026-01193-4","url":null,"abstract":"PROTEUS met its amended co-primary end points but should not be interpreted as practice changing. The trial compared two experimental strategies rather than the current standard of care, relied on an unvalidated approach (prostate-specific membrane antigen-PET) for assessments of metastasis-free survival, demonstrated minimal absolute benefit with increased toxicity and lacks both mature overall survival data and sufficient data on patient-reported outcomes to support adoption.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 11","pages":"827-828"},"PeriodicalIF":94.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713308","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 proteome comes of age, but precision oncology needs functional maps","authors":"Emanuel Petricoin, Thomas Conrads, Lance Liotta","doi":"10.1038/s41571-026-01196-1","DOIUrl":"10.1038/s41571-026-01196-1","url":null,"abstract":"Yue and colleagues present a landmark anatomical atlas of human protein abundance across non-malignant tissues and cancers. We argue that precision oncology needs functional proteomic maps that add signalling activity, post-translational modifications, pathology-guided compartment resolution, metastatic and longitudinal sampling, clinical annotation and population diversity to make proteomics therapeutically actionable.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 11","pages":"823-824"},"PeriodicalIF":94.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707261","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":"HCT–ASCT confirmed as standard-of-care consolidation therapy for PCNSL","authors":"David Killock","doi":"10.1038/s41571-026-01197-0","DOIUrl":"10.1038/s41571-026-01197-0","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 10","pages":"738-738"},"PeriodicalIF":94.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689678","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":"AI-based augmentation of oncology clinical trials","authors":"Andrea Villa, Ashley L. Eadie, David Synnott, Rebecca Romanò, Max Piffoux, Evelyn Yi Ting Wong, Naomi Scheinerman, Daniel S. W. Tan, Filippo Guglielmo Maria de Braud, Miriam Koopman, Jarushka Naidoo, Madhusmita Behera, Selen Bozkurt, Susan Halabi, Rodrigo Dienstmann, Loic Verlingue, Arsela Prelaj, Ravi B. Parikh","doi":"10.1038/s41571-026-01189-0","DOIUrl":"10.1038/s41571-026-01189-0","url":null,"abstract":"Oncology clinical trials are often characterized by slow accrual, high failure rates and limited generalizability, reflecting both biological complexity and operational inefficiencies. Advances in artificial intelligence (AI) — enabled by large-scale electronic health record datasets and machine learning methods — offer new opportunities to address these challenges across the clinical trial lifecycle. In this Review, we discuss applications of AI across pre-trial design, trial conduct, and post-trial inference and generalization, highlighting how these tools can improve trial feasibility, support patient engagement and extend the relevance of trial findings. We also address cross-cutting challenges related to equity, data quality and drift, transparency, and regulatory oversight. The most immediate and evidence-supported role of AI in oncology trials lies in augmenting operational workflows under human oversight, particularly in the identification of candidate patients for enrollment, eligibility assessment, data extraction and trial monitoring (including remote patient and/or safety monitoring as well as monitoring of AI model performance and real-time trial data extraction) — applications that are now being implemented at select cancer centres. By contrast, AI applications designed to replace clinical evidence generation, such as synthetic control arms, outcome-prediction simulations and digital twins, remain at earlier stages of development, with limited prospective validation and unresolved methodological and regulatory challenges. Ultimately, we argue that achieving the potential of AI in oncology clinical trials will require rigorous prospective validation, harmonized regulatory standards, and coordination among clinicians, trialists, regulators, industry and patients. Oncology clinical trials are characterized by high failure rates — reflecting both the biological complexity of cancer and operational inefficiencies — and the generalizability of their results is often limited. In this Review, the authors discuss opportunities to address these limitations via application of artificial intelligence tools across the lifecycle of clinical trials as well as key challenges that must be overcome for routine clinical deployment of these tools.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 11","pages":"831-848"},"PeriodicalIF":94.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689716","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":"Benefit from perioperative enfortumab vedotin–pembrolizumab in cisplatin-eligible MIBC","authors":"Diana Romero","doi":"10.1038/s41571-026-01195-2","DOIUrl":"10.1038/s41571-026-01195-2","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 10","pages":"737-737"},"PeriodicalIF":94.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673839","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":"More options, more questions in the management of early relapsed and/or refractory multiple myeloma","authors":"Carlyn Rose Tan, Sham Mailankody","doi":"10.1038/s41571-026-01191-6","DOIUrl":"10.1038/s41571-026-01191-6","url":null,"abstract":"In MonumenTAL-3, the G-protein-coupled receptor class C group 5 memberD-directed bispecific T cell engager talquetamab combined with either daratumumab or daratumumab–pomalidomide conferred significantly longer progression-free survival than daratumumab–pomalidomide–dexamethasone in patients with relapsed and/or refractory multiple myeloma (≥1 prior line of therapy). These results herald a new therapeutic option for such patients but also raise questions regarding how talquetamab-based regimens should be integrated with B cell maturation antigen-directed T cell-redirecting therapies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 10","pages":"741-742"},"PeriodicalIF":94.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648862","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":"Clinical toxicity of ADCs and ICI–ADC combinations: mechanisms, patterns and management","authors":"Solange Peters, Petros Grivas, Christophe Massard, Sara M. Tolaney, Michel Obeid","doi":"10.1038/s41571-026-01188-1","DOIUrl":"10.1038/s41571-026-01188-1","url":null,"abstract":"Antibody–drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) have reshaped cancer therapy both as monotherapy and in combination. However, these drug classes have toxicity profiles that, despite arising from different biological mechanisms, often converge on the same organs. Given that ICI–ADC combinations are moving into earlier lines of treatment, including curative-intent settings, clinicians increasingly face overlapping pulmonary, hepatic, gastrointestinal and cutaneous adverse events with uncertain attribution, and the management of toxicities during the acute event and subsequent treatment resumption and the management of rechallenge after toxicity resolution remain variable. In this Review, we propose a unified, mechanism-informed framework that links three interacting layers: immune activation, payload cytotoxicity and payload-independent effects (from target, platform and host-related determinants). We compare organ-level patterns across major payload classes, highlight consistent organ signatures and provide practical algorithms for evaluation, initial management and treatment resumption in patients receiving ADC monotherapy or ICI–ADC combinations. Finally, we propose minimum reporting standards to harmonize toxicity phenotyping and enable cross-trial comparisons, biomarker discovery and the development of safer regimens. With the expanded use of antibody–drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) in combination, clinicians increasingly face overlapping toxicity profiles with uncertain attribution. The authors of this Review propose a framework that links three interacting layers: immune activation, payload cytotoxicity and payload-independent effects, and provide practical algorithms for evaluation, initial management and treatment resumption in patients receiving ADC monotherapy or ICI–ADC combinations.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 10","pages":"806-821"},"PeriodicalIF":94.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41571-026-01188-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631059","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}

{"title":"De-escalation trials in multiple myeloma: past, present and future","authors":"Hira Mian, Luciano J. Costa, Mohamad Mohty, Alfred Garfall, S. Vincent Rajkumar","doi":"10.1038/s41571-026-01186-3","DOIUrl":"10.1038/s41571-026-01186-3","url":null,"abstract":"De-escalation of therapy constitutes a new phase in the development of therapeutic approaches for patients with multiple myeloma (MM) and is aimed at maintaining durable disease control while reducing the toxicity and burden associated with prolonged treatment. Given that increasingly effective agents, including immunotherapies, are now used earlier in the course of MM, we must assess not only how much therapy is needed to enable a clinical response but also how much is required to sustain it. In this Review, we synthesize emerging evidence supporting multiple de-escalation strategies, including dose and schedule modification, withdrawal of individual agents from multidrug regimens, fixed-duration approaches with treatment-free intervals, minimal residual disease-adapted strategies, omission of autologous stem cell transplantation and single infusion of chimeric antigen receptor T cells. We highlight how contemporary trials are beginning to define the patient populations and treatment components most amenable to de-escalation while exposing ongoing uncertainties and challenges, including those relating to monitoring strategies, re-treatment criteria and feasibility. Finally, we discuss methodological and implementation challenges including end point selection, clinical trial design, integration of correlative translational research, funding models and the involvement of key stakeholders required to translate de-escalation approaches from concept to a clinical trial and, eventually, routine clinical practice. Current treatment approaches for patients with multiple myeloma are characterized by a ‘more is better’ philosophy aiming for deep and long-term clinical responses. The authors of this Review challenge this paradigm, presenting several de-escalation strategies that do not compromise long-term efficacy and proposing a framework for the design of trials testing further de-escalation approaches.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 10","pages":"792-805"},"PeriodicalIF":94.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620807","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":"Electronic cigarettes, smoking and lung cancer risk: some evidence about the continuum of harm","authors":"Peter G. Shields","doi":"10.1038/s41571-026-01192-5","DOIUrl":"10.1038/s41571-026-01192-5","url":null,"abstract":"Since the introduction of vaping with electronic cigarettes in the late 2000s, controversy has continued to exist regarding the risks and benefits. Many studies indicate that electronic cigarettes are an effective smoking-cessation tool. Now, a large database analysis by Kim et al. provides a glimpse of the risks of lung cancer for smokers who quit with versus without vaping.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 10","pages":"735-736"},"PeriodicalIF":94.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605495","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}