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Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for developing extra-hepatic cancers. Now, Li et al. uncover an exosome-driven metabolic connection between the steatotic liver and the breast that fosters cancer progression.
Large biobank projects such as FinnGen have enabled systematic searches for inherited factors that causally influence a wide range of human traits, including cancer risk and outcome. These explorations provide genetic insights for various aspects of cancer research, including improved risk prediction, enhanced biomarker and drug target discovery, and personalized medicine.
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 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.
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.
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 Journal Club, Bansal and Mazumder discuss a study that investigated the interplay between three-dimensional genome structure and mutational load in cancer.
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.
Lyons et al. explored the rules of specificity and function for condensates formed by oncogenic fusion proteins, and identified a common molecular signature in these oncoproteins that compartmentalizes RNA polymerase II to confer an increase in gene activation and consequent cancer phenotypes.
In a recent study published in Nature, Liu, Wang, et al. investigate the mechanisms underlying cytarabine-induced neurotoxicity and provide a mechanistic explanation for the differing neurotoxicity profiles of other nucleoside analogues, such as gemcitabine.
In a study published in Cell, Phelps et al. find a mechanism connecting exercise, gut microbiota and anti-tumour immunity; exercise induces microbiota to produce formate, which in turn enhances CD8+ T cell functionality.
In this Journal Club, Halder and Srivastava discuss a study that investigated how activation-induced deaminase (AID)-mediated DNA double-strand breaks lead to translocations in a cell type-specific manner.
Rising rates of early-onset oestrogen receptor-positive (ER+) breast cancer in women without genetic risk suggest a shift in disease biology. Endocrine-disrupting chemicals (EDCs) may accelerate tissue ageing, destabilize epigenetic regulation and impair immune surveillance. Chronic and cumulative EDC exposure may induce field cancerization in the breast, warranting urgent attention from researchers, regulators and public health leaders.
In this Tools of the Trade article, Jess Hebert describes the development and use of Cas12a mice for the unbiased, high-throughput generation and interrogation of complex tumour genotypes.
