Articles in 2025

Although ferroptosis, an iron-dependent form of regulated cell death, is emerging as a therapeutic vulnerability in cancer, clinical translation is hindered by context-dependent regulation, a lack of predictive biomarkers and challenges in clinical trial design. In this Review, Wahida and Conrad examine the biological basis of ferroptosis, including its immunogenic potential, and outline the necessary steps towards translating ferroptosis-based therapies into the clinic.

Antibody–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.

Urine-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.

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.

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.

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.

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.

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.

In this Review, Kennel and Greten highlight the role of immune cells in colorectal cancer (CRC) development, progression and metastasis as well as the impact of therapies on the immune microenvironment. They emphasize the need for novel strategies to enhance immunogenicity and CRC patient stratification to improve outcomes.

Glucagon-like peptide-1 (GLP-1) receptor agonists are widely prescribed for weight loss. Here, Hebert and colleagues discuss the need for long-term studies assessing the impacts of this on muscle mass and nutritional deficiencies, which may influence cancer susceptibility and metabolic health.

Neurotoxicity impacting the central and peripheral nervous systems is a considerable adverse effect of both conventional and novel cancer therapies. In this Review, Karschnia et al. outline what is currently known about the mechanisms that underlie the clinical symptoms of central nervous system injury and peripheral neuropathy and the ongoing development of interventions to treat and prevent this unmet medical need.

In a recent study, Salomó Coll et al. demonstrate that impaired ER-phagy in Kras-mutant pancreatic acinar cells leads to the accumulation of protein aggregates and disruption of acinar cell homeostasis, thereby cooperating with oncogenic KRAS to promote cellular transformation.

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 Journal Club, Bansal and Mazumder discuss a study that investigated the interplay between three-dimensional genome structure and mutational load in cancer.

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.

Chia, Johnson et al. outline a mechanism for how pulmonary viral infections can awaken dormant disseminated cancer cells to enhance metastatic burden.

Allogeneic haematopoietic stem cell transplantation remains the cornerstone of curative treatment for advanced myeloid malignancies. In this Perspective, Foldvari et al. propose that T cells engineered to express tumour-reactive T cell receptors (TCRs) may offer a safer and more effective alternative. They outline key considerations for identifying and validating suitable target antigens and matching TCRs, and for advancing these therapies towards clinical application.

Recent extreme weather events have impacted communities once considered safe from climate hazards, posing growing challenges to cancer control efforts. Here, Nogueira and Salas argue that the oncology community urgently needs to prioritize solution-focused adaptation and mitigation actions.

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.