Osorio et al. report a first-in-human study of intratumoral 2141-V11, an Fc-engineered CD40 agonistic antibody, showing it is safe and induces systemic and durable antitumor immunity in patients with metastatic cancer. 2141-V11 also promotes tertiary lymphoid structure formation and CD8+ T cell activation, overcoming limitations of prior CD40 agonists.

Nature Reviews Cancer, Published online: 15 October 2025; doi:10.1038/s41568-025-00879-8In 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.

Ma et al. discovered that the disruption of mitochondrial dynamics impairs ATP generation and activates AMPK, which phosphorylates NRF2, facilitating its translocation to the nucleus. Within the nucleus, NRF2 drives FSP1 expression and confers resistance to ferroptosis. They also identified that mitochondrial fusion promoter M1 mitigates doxorubicin-induced chemotoxicity.

Zhou et al. show that creatine sensitizes cancer cells to ferroptosis by impairing ERK2 activation, thereby inhibiting ERK2-mediated stabilization of FSP1. Combining creatine supplementation with targeting PD-1 synergistically enhances anti-tumor immunity in mice. These results suggest that creatine activates ferroptosis, induces tumor suppression, and enhances ferroptosis-based treatments for CRC.

Nature Reviews Cancer, Published online: 08 September 2025; doi:10.1038/s41568-025-00868-xIn 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.

(Molecular Cell 84, 4645–4659.e1–e9; December 5, 2024)

Liu et al. demonstrate that lysosomal inhibitors can block CDI ferroptosis independently of autophagy and that clathrin-mediated endocytosis of transferrin is essential for cysteine-deprivation-induced (CDI) ferroptosis by sustaining cellular iron. This study also reveals fundamental differences between CDI ferroptosis and that induced by GPX4 inhibition.

Gao and colleagues identify new therapeutic opportunities for pancreatic cancer via integrated pharmacogenomic analysis of organoid models, highlighting statins as effective agents to overcome chemoresistance and offering translational insights for refractory PDAC treatment.

Thinking about applying for an ERC grant? In this video, Line Volkers, Call Coordinator at the ERC, shares key advice on how to get started, from what makes an ERC grant unique to the essential steps…

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources s...

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.

Succulents become rechargeable night lights after injection with tiny phosphor particles.

Lin et al. discover homocysitaconate, an anti-inflammatory metabolite formed during inflammation via AHCY-catalyzed adduction of homocysteine and itaconate. Homocysitaconate is recognized by MARS, inducing an N-homocysteinylation metabolic shift that leads to NLRP3 inhibition. Exogenous homocysitaconate supplementation and endogenous homocysitaconate boosting (via NAD+-dependent AHCY activation) offer novel therapeutic strategies for inflammatory disorders.

New findings strengthen the link between retinal health and early dementia risk.

Liu et al. demonstrate that lysosomal inhibitors can block CDI ferroptosis independently of autophagy and that clathrin-mediated endocytosis of transferrin is essential for cysteine-deprivation-induced (CDI) ferroptosis by sustaining cellular iron. This study also reveals fundamental differences between CDI ferroptosis and that induced by GPX4 inhibition.

Yao et al. identify C19orf12 as an oncogene in NSCLC, promoting metastasis, glucose metabolic reprogramming, and mitochondrial dysfunction. C19orf12 binds LRPPRC and inhibits mitochondrial ETC complex I and IV. NSCLC cells with elevated C19orf12 expression levels are associated with therapeutic sensitivity to metformin.

Li et al. find that the abrogation of amino acid sensing by Ubr1 induces lipid droplet accumulation as a protective response against oxidative stress. Lipid peroxidation during oxidative stress generates 4-hydroxynonenal, which directly inactivates Hsc70-4, the ATPase needed to maintain Ubr1 responsiveness and downstream control of lipolysis.

As teams grow, new Ph.D. graduates are less likely to land tenure-track jobs and more likely to leave science—especially women and international researchers

Radiotherapy (RT), while pivotal in cancer control, may paradoxically promote metastasis through systemic effects. Emerging evidence implicates RT-induced growth factors and immune modulation—especially via amphiregulin-epidermal growth factor receptor (EGFR) signaling—in facilitating metastatic outgrowth at distant sites. This effect underscores the need to refine RT strategies, identify high-risk patients, and explore therapeutic combinations targeting myeloid cells and EGFR pathways to mitigate pro-metastatic consequences and optimize outcomes in the immunotherapy era.