{"title":"From detection to direction: ctDNA-guided personalized therapy for muscle-invasive bladder cancer","authors":"Britt B. M. Suelmann, Michiel S. van der Heijden","doi":"10.1038/s41571-025-01113-y","DOIUrl":"10.1038/s41571-025-01113-y","url":null,"abstract":"Despite radical cystectomy, residual urothelial cancer cells can persist undetected in patients with muscle-invasive bladder cancer, silently seeding future relapse. New data from the phase III IMvigor011 trial demonstrate that circulating tumour DNA (ctDNA) can be used to effectively stratify patients by recurrence risk, enabling adjuvant atezolizumab to be delivered selectively to those who are likely to benefit. This precision ctDNA-guided strategy might fundamentally reshape postoperative management through alignment of treatment intensity with molecular risk.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 3","pages":"155-156"},"PeriodicalIF":82.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759909","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}
Firas El Chaer, Jan P. Bewersdorf, Maximilian Stahl, Amer M. Zeidan
{"title":"The global epidemiology of acute myeloid leukaemia","authors":"Firas El Chaer, Jan P. Bewersdorf, Maximilian Stahl, Amer M. Zeidan","doi":"10.1038/s41571-025-01099-7","DOIUrl":"10.1038/s41571-025-01099-7","url":null,"abstract":"Acute myeloid leukaemia (AML) is an aggressive haematological malignancy with an incidence that increases with age and varies widely across regions owing to differences in risk factors, diagnostic capabilities, recording in cancer registries and access to health care. Despite improved outcomes over the past decade owing to the approvals of various novel therapies as well as improvements in supportive care and better access to, and safety of, allogeneic haematopoietic stem cell transplantation, progress has largely been confined to high-income countries. Patients in low-income or middle-income countries often remain reliant on older cytotoxic regimens, when available. The incidence of AML in high-income countries has increased over the past decades owing to population ageing in many of these countries as well as improved access to diagnostics. By contrast, AML has a lower incidence but is associated with higher mortality and morbidity in most low-income or middle-income countries. Multiple risk factors predispose individuals to AML, including germline variants, environmental and lifestyle factors, prior exposure to chemotherapy and radiation, and certain medical conditions and comorbidities. In this Review, we highlight global trends in the incidence, risk factors, demographic disparities and treatment-related outcomes of patients with AML across diverse geographical regions. We also outline the urgent need to improve the cancer registry infrastructure, expand global surveillance, leverage artificial intelligence for data analysis and promote equitable access to clinical trials. Despite the availability of various novel therapies, the global incidence of acute myeloid leukaemia (AML) has continued to increase. Owing to a combination of population ageing and more effective diagnosis, AML remains much more common in economically developed countries. Conversely, AML is less common in the economically developing world, albeit often with worse outcomes owing to a lack of access to effective therapies. In this Review, the authors describe these global trends as well as their underlying reasons, including the changing landscape of risk factors, demographic disparities and differing treatment outcomes.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"107-120"},"PeriodicalIF":82.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680359","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":"When ctDNA says ‘maybe’: improving the dynamics of MRD trials","authors":"Julien Taieb","doi":"10.1038/s41571-025-01111-0","DOIUrl":"10.1038/s41571-025-01111-0","url":null,"abstract":"Circulating tumour DNA (ctDNA) has emerged as a promising biomarker enabling the detection of minimal residual disease (MRD) in patients with locally advanced colon cancer. The phase II/III DYNAMIC-III trial, with results recently reported, is a landmark effort to evaluate ctDNA-guided adjuvant treatment in this setting. Here, I discuss how, despite not yet changing clinical practice, these results provide essential insights to guide the next generation of ctDNA-driven trials.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 3","pages":"153-154"},"PeriodicalIF":82.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645145","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}
Zev A. Binder, Stephen J. Bagley, Jessica B. Foster, Donald M. O’Rourke
{"title":"The development of CAR T cells for patients with CNS malignancies","authors":"Zev A. Binder, Stephen J. Bagley, Jessica B. Foster, Donald M. O’Rourke","doi":"10.1038/s41571-025-01102-1","DOIUrl":"10.1038/s41571-025-01102-1","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells have become standard-of-care therapies for patients with certain relapsed and/or refractory haematological malignancies over the past decade. However, this approach remains largely ineffective in patients with solid tumours, in part owing to limited CAR T cell persistence, the immunosuppressive tumour microenvironment of many solid tumours and limited trafficking of CAR T cells into tumours. Central nervous system (CNS) tumours, many of which are associated with a poor prognosis and require new treatment approaches, present additional challenges such as the presence of the blood–brain barrier as well as concerns over treatment-related neurotoxicities. Despite these difficulties, clinical trials involving both adult and paediatric patients with primary CNS tumours have provided signals of efficacy. In this Review, we discuss completed, ongoing and anticipated trials testing CAR T cells in patients with CNS tumours. We also highlight the most promising preclinical developments that might lead to novel clinical approaches in this area. Despite advances in the treatment of many advanced-stage solid tumours, the outcomes of patients with central nervous system tumours have not improved substantially for several decades, largely owing to a lack of novel therapies. In this Review, the authors describe the clinical experience with chimeric antigen receptor T cells both in adults and children with these historically difficult to treat malignancies, including some promising signals of efficacy.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"137-150"},"PeriodicalIF":82.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645147","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}
Michael A. Cilento, Lisa M. Butler, Louise Emmett, Christopher J. Sweeney
{"title":"Personalized intensification of treatment for hormone-sensitive prostate cancer","authors":"Michael A. Cilento, Lisa M. Butler, Louise Emmett, Christopher J. Sweeney","doi":"10.1038/s41571-025-01100-3","DOIUrl":"10.1038/s41571-025-01100-3","url":null,"abstract":"Historically, systemic therapy for hormone-sensitive prostate cancer (HSPC) was predicated on androgen-deprivation therapy (ADT) alone. However, in the past decade, substantial improvements have been made by intensifying treatment based on a better understanding of the broad underlying biology of these cancers. The addition of androgen receptor pathway inhibitors (ARPIs), docetaxel and/or radiotherapy to ADT is of proven benefit in certain patient subgroups, whereas AKT inhibitors, radioligand therapies and poly ADP-ribose polymerase (PARP) inhibitors are being evaluated in patients with metastatic HSPC. The clinical states of HSPC are determined by a history of localized prostate cancer versus presentation with de novo metastatic disease, as well as the extent of disease on conventional computed tomography imaging and whole-body bone scintigraphy. However, modern nuclear imaging modalities such as prostate-specific membrane antigen PET can visualize metastases below the limit of detection of computed tomography and whole-body bone scintigraphy; this earlier and more precise detection of metastases has identified new subgroups of patients for which certain treatment approaches, such as adding docetaxel to ADT plus an ARPI, might or might not apply. In this Review, we discuss the personalized management of both non-metastatic and metastatic HSPC, including how to select patients for docetaxel, choice of ARPI and use of radiotherapy to primary and metastatic disease sites. We also discuss emerging novel therapies and important principles of toxicity mitigation for HSPC. Advances in the management of hormone-sensitive prostate cancer have been achieved through intensification of therapy, although careful patient selection is required. In this Review, the authors discuss personalized treatment strategies for both non-metastatic and metastatic hormone-sensitive prostate cancer, as well as emerging novel therapies and key principles for toxicity mitigation.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"121-136"},"PeriodicalIF":82.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609149","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}
Sara Coca Membribes, Bernadett Szabados, Thomas Powles
{"title":"Towards biomarker-driven therapies for urothelial carcinoma","authors":"Sara Coca Membribes, Bernadett Szabados, Thomas Powles","doi":"10.1038/s41571-025-01095-x","DOIUrl":"10.1038/s41571-025-01095-x","url":null,"abstract":"Molecularly targeted agents and immune checkpoint inhibitors (ICIs) are transforming the treatment landscape for patients with advanced-stage urothelial carcinoma (aUC), although trials testing these novel agents have shown mixed results. In this context, the identification of biomarkers has seen limited success: while activating mutations in FGFR3 are now established as an actionable biomarker to guide treatment with FGFR inhibitors, PD-L1 expression has shown inconsistent value as a predictive biomarker of response to ICIs. The identification of prognostic and predictive biomarkers for ICIs, antibody–drug conjugates and targeted therapies is an active area of research; promising candidates include tumour mutational burden and HER2 overexpression. In the past few years, circulating tumour DNA has emerged as a minimally invasive biomarker, with increasing data supporting its prognostic value and utility for monitoring clinical responses. In this Review, we address these developments and discuss biomarkers that could have clinical utility in patients with aUC. The identification of prognostic and predictive biomarkers for immune checkpoint inhibitors, antibody–drug conjugates and targeted therapies for urothelial carcinoma is currently an active area of research. In this setting, circulating tumour DNA is emerging as a minimally invasive biomarker with utility for monitoring clinical responses. The authors of this Review discuss biomarkers that could have clinical utility in patients with this malignancy","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"92-106"},"PeriodicalIF":82.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609150","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}
Milit S. Patel, Edward Christopher Dee, Nancy Y. Lee
{"title":"AI and human expertise in cancer care — striving for synergy","authors":"Milit S. Patel, Edward Christopher Dee, Nancy Y. Lee","doi":"10.1038/s41571-025-01108-9","DOIUrl":"10.1038/s41571-025-01108-9","url":null,"abstract":"Artificial intelligence (AI) excels at rapid data synthesis and pattern recognition, yet the practice of oncology demands nuanced clinical judgement, ethical reasoning and authentic empathy — qualities only humans can provide. The future of cancer care lies in synergy: AI augmenting human expertise, not replacing it. Excellence emerges when computational power meets clinical wisdom.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"87-88"},"PeriodicalIF":82.2,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593613","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":"Could a COVID-19 vaccine improve the effectiveness of cancer immunotherapy?","authors":"Sacha Gnjatic","doi":"10.1038/s41571-025-01105-y","DOIUrl":"10.1038/s41571-025-01105-y","url":null,"abstract":"A recent Nature article reports that mRNA vaccines against SARS-CoV-2 confer improved survival among patients with advanced-stage non-small-cell lung cancer or melanoma receiving immune-checkpoint inhibitors owing to activation of systemic immunity, potentiating antitumour responses. This retrospective proof-of-principle study indicates the potential for combined therapeutic interventions, although both the timing of vaccination as well as the nature of the elicited immune responses requires further investigation.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"90-91"},"PeriodicalIF":82.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554116","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}