In this Journal Club, Lopez-Hernandez and Ortega-Del Vecchyo discuss a study that mapped the genetic basis of hybrid incompatibility in swordtail fish, revealing melanoma-causing gene interactions that reduce survival in natural hybrid populations.

This Review by Imianowski et al. outlines the various contributions that regulatory T cells, present in the tumour microenvironment, make towards tumour progression and highlight the ways in which they represent attractive next-generation immunotherapeutic targets.

The 2025 Nobel Prize in Physiology or Medicine has been awarded jointly to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries ...

The outcomes for patients with cancer of unknown primary have improved through the use of molecularly guided therapies, for those both with and without a presumptive tissue-of-origin diagnosis. Genomic testing followed by molecularly guided therapies significantly improves survival compared to empiric chemotherapy, highlighting its practice-changing potential.

In a study published in Nature Immunology, Fuentes et al. demonstrate that the pre-T cell receptor (TCR) is expressed in leukaemia-initiating cells in patients with T cell acute lymphoblastic leukaemia, and that targeting it can inhibit tumour progression.

Nature Reviews Cancer, Published online: 02 October 2025; doi:10.1038/s41568-025-00869-wAntibody–drug conjugates are rapidly expanding both in the clinical treatment of cancer and in preclinical development. In this Review, Zippelius et al. highlight the molecular interactions and immune system effects of these sophisticated drugs that drive their efficacy and toxicity.

In a recent study published in Nature Genetics, Kübler, Nardone et al. analysed the mechanisms underlying tamoxifen-associated uterine cancer and identified PI3K pathway activation as a key non-genetic driver.

In this Review, Dong and Blanpain outline our current understanding of the epithelial-to-mesenchymal transition in cancer, which we now know is not a simple binary switch but the existence of a series of different tumour states. The authors also discuss the implications of this knowledge for pharmacologically targeting epithelial-to-mesenchymal transition to overcome therapy resistance.

Nature Reviews Cancer, Published online: 26 September 2025; doi:10.1038/s41568-025-00881-0In a recent study published in Nature Genetics, Kübler, Nardone et al. analysed the mechanisms underlying tamoxifen-associated uterine cancer and identified PI3K pathway activation as a key non-genetic driver.

Nature Reviews Cancer, Published online: 25 September 2025; doi:10.1038/s41568-025-00873-0In this Review, Dong and Blanpain outline our current understanding of the epithelial-to-mesenchymal transition in cancer, which we now know is not a simple binary switch but the existence of a series of different tumour states. The authors also discuss the implications of this knowledge for pharmacologically targeting epithelial-to-mesenchymal transition to overcome therapy resistance.

In this Perspective, de Magalhães explores the evolutionary relationship between cancer and ageing, proposing that the need to minimize cancer risk early in life may contribute to tissue degeneration later on, representing a trade-off that constrains the evolution of longer lifespans.

In this Perspective, Lazure and Gomes argue that metabolic changes that occur as a result of ageing may shape tumour initiation and progression and the development of metastatic disease.

In this Review, Easwaran and Weeraratna outline how ageing leads to epigenetic alterations in the tissue microenvironment, enhancing clonal expansion of mutations and ultimately increasing cancer risk.

In this Review, Henry and DeGregori discuss the contributions of the various models and methods used to study the connection between ageing and cancer, highlighting the strengths and limitations of those models and technologies, as well as advocating for the wider adoption of age-appropriate models of cancer to improve our clinical translation of approaches to prevent and treat human cancers.

Ageing influences cancer risk through cellular and environmental changes, including the induction of cellular senescence. In this Review, Ye, Melam and Stewart highlight the role of senescent stromal cells in cancer and the therapeutic implications of this.

Ageing reshapes immune composition, function and regenerative capacity, with profound effects on tumour immunity, cancer progression and treatment outcomes. In this Review, Dolan and colleagues examine how age-resolved immunoprofiling, insights from ageing haematopoiesis and preclinical modelling are uncovering immune ageing dynamics and therapeutic challenges — revealing new opportunities to optimize cancer therapy across diverse age groups.

In this Tools of the Trade article, Kenta Ninomiya describes the development of ImAge, an imaging-based approach that captures age-related trajectories of chromatin and epigenetic marks in single nuclei for longitudinal analyses.

Understanding the complex relationship between ageing and cancer is crucial for cancer risk prediction. In this Comment, LaBarge and Binder explore how tissue-specific ageing biomarkers can enhance cancer risk stratification and highlight the need for tailored approaches in assessing susceptibility across different tissues.

While cancer treatments are essential for patient survival, they often induce premature ageing-related conditions in survivors. In this Comment, Demaria outlines how understanding the underlying molecular mechanisms of this is crucial for developing integrated strategies to improve long-term health outcomes in survivors.

Ageing is a fundamental driver of cancer, fostering the accumulation of genetic and epigenetic changes that disrupt cellular homeostasis, promote immune ...

Nature Reviews Cancer, Published online: 25 September 2025; doi:10.1038/s41568-025-00882-zUrine-based tumour DNA detection enables non-invasive profiling of urological malignancies and may inform on distant cancers via trans-renal cell-free DNA (cfDNA). Here the authors propose the ‘minimal urine methods in experiments’ (MUMIE) framework to enhance validation and standardization of urinary cfDNA biomarkers.

Nature Reviews Cancer, Published online: 24 September 2025; doi:10.1038/s41568-025-00877-wThe outcomes for patients with cancer of unknown primary have improved through the use of molecularly guided therapies, for those both with and without a presumptive tissue-of-origin diagnosis. Genomic testing followed by molecularly guided therapies significantly improves survival compared to empiric chemotherapy, highlighting its practice-changing potential.

This Focus issue highlights current research at the intersection of ageing and cancer, and explores how insights gained from this may lead to better cancer prevention strategies and diagnostics, enhanced therapeutic efficacy and improvements to both patient quality of life and outcomes.

Nature Reviews Cancer, Published online: 24 September 2025; doi:10.1038/s41568-025-00884-xIn this Journal Club, Lopez-Hernandez and Ortega-Del Vecchyo discuss a study that mapped the genetic basis of hybrid incompatibility in swordtail fish, revealing melanoma-causing gene interactions that reduce survival in natural hybrid populations.