Articles in 2025

A study published in Science shows that liver zonation shapes hepatocellular carcinoma (HCC) development. In mice, HCC predominantly originates from zone 3 hepatocytes, where GSTM2 and GSTM3 drive initiation by inhibiting ferroptosis, revealing metabolic vulnerabilities in liver cancer.

Patient and public involvement and engagement (PPIE), although well established in clinical settings, remains less well defined in laboratory-based settings, where infrastructure to support meaningful collaboration is limited. In this Comment, the authors propose a novel framework for embedding PPIE ambassadors into basic cancer research pipelines, outlining strategies to address power imbalances, enhance communication and facilitate knowledge translation.

Macrophages can eliminate cancer cells through phagocytosis, which is tightly regulated through inhibition and activation of various phagocytic receptors. In this Review, Veillette and colleagues outline how targeting these phagocytic checkpoints could be harnessed therapeutically, address therapeutic efficacy concerns, and propose strategies to enhance therapeutic outcomes in future clinical applications.

In this Review Luo, Kharas and Jaffrey outline how N⁶-methyladenosine (m⁶A) RNA modification affects RNA stability, translation, splicing and immune responses to influence cancer biology. They discuss emerging evidence on how m⁶A may influence cancer metabolic reprogramming and outline the challenges and opportunities of targeting m⁶A writers, erasers and readers for cancer therapy.

Concomitant medications are emerging as a modifiable prognostic factor for immune checkpoint inhibitor treatment outcomes. This Review by Stone et al. highlights the potential immunomodulatory interactions of commonly prescribed medications and supplements, and proposes strategies to make better use of this information to guide clinical care.

Tumour heterogeneity has a substantial impact on tumour progression and treatment response, yet bulk expression data obtained from clinical tumour samples obscure this complexity. Computational deconvolution methods can resolve cell-type-specific signals. This Review offers a practical guide for cancer researchers to select deconvolution methods and maximize the utility of bulk transcriptomic data.

A common side effect of treatment with taxane-based chemotherapy is peripheral neuropathy. Now, Fonseca et al. uncover the endoplasmic reticulum (ER) stress response in leukocytes as the effective mediator of paclitaxel-induced peripheral nerve damage.

Macropinocytosis enables cancer cells to absorb nutrients from their environment, supporting growth and therapy resistance. In this Review, Tang, Wang, Kroemer and Kang outline its regulatory mechanisms, implications for treatment strategies and potential as a target for enhancing therapeutic efficacy in oncology.

In this Journal Club, Basurto-Lozada and Robles-Espinoza discuss a study that challenges the prevailing view of a monoclonal origin of cancer by showing that early lesions in mouse models of colorectal cancer are polyclonal.

Neutrophil extracellular traps (NETs) influence cancer initiation, progression and metastasis through immunosuppressive mechanisms within the tumour microenvironment. In this Review, Shahzad et al. highlight our recent understanding of NET biology in cancer and emphasize both the translational data available and the need for further clinical trials evaluating NETs and NET-directed therapies.

In a recent study, Mohri et al. reveal how melanocyte stem cells integrate distinct genotoxic signals through niche-derived KITL to drive either hair greying or melanomagenesis.

Transcriptional and epigenetic mechanisms governing T cell exhaustion substantially impact immunotherapy effectiveness. In this Review, Kang et al. outline epigenetic regulatory programmes that influence T cell differentiation fates, proposing strategies to enhance clinical outcomes and immunotherapy durability in cancer through improved understanding of T cell biology.

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.

FLASH radiotherapy demonstrates reduced complications in healthy tissues while effectively targeting tumours. In this Perspective, Vozenin et al. review the clinical implications, mechanistic basis and provide novel hypotheses for FLASH efficacy.

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 this Review, Mao et al. discuss the regulation and interplay of the metabolic cell death pathways ferroptosis, disulfidptosis and cuproptosis and explore how these mechanisms can be harnessed for cancer therapies.

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.