In a recent study published in Nature, Natarajan et al. uncover a metabolic–epigenetic circuit in which glutamine-derived itaconate functions as an oncometabolite to sustain oncogenic ZFTA–RELA expression in ependymoma. Disrupting this pathway lowers ZFTA–RELA levels and suppresses tumour growth in preclinical models, revealing a promising therapeutic vulnerability in this aggressive cancer.

Colitis predisposes to colorectal cancer, but how inflammation promotes tumour initiation has remained unclear. Nagaraja et al. show that inflammatory injury imprints a heritable epigenetic memory in colonic stem cells that enhances AP-1-driven proliferative programs and accelerates malignant outgrowth following oncogenic mutation.

Mutant haematopoietic stem cells display broad fitness variation, suggesting that protective mechanisms may limit clonal expansion and malignant transformation. Now, Agarwal et al. identify a germline noncoding variant that confers resilience to clonal haematopoiesis of indeterminate potential (CHIP) by dampening expression of the RNA-binding protein MSI2.

The 2026 annual meeting of the American Association for Cancer Research (AACR) was held under the theme ‘Precision, Partnership, Purpose: Advancing Cancer Science to Save Lives Globally’. Here, we summarize some key highlights from the meeting.

In a recent study, Gudenas et al. map pineoblastoma subgroups to pinealocyte progenitors and identify a shared photoreceptor-like transcriptional network across pineoblastoma, retinoblastoma and group 3 medulloblastoma, revealing a developmental vulnerability with therapeutic potential.

A recent study identifies TEX264-dependent nucleophagy as an important mechanism that mediates the clearance of trapped PARP1, thereby limiting PARP1-induced toxicity and promoting resistance to PARP inhibitors.

Megakaryocytes contribute substantially to the pathogenesis of myeloproliferative neoplasms (MPNs), but therapeutic strategies targeting this lineage are lacking. Wen, Cotton et al. demonstrate that menin inhibition impairs megakaryocyte differentiation, suppresses myelofibrosis and improves disease features across preclinical MPN models.

In a recent study, Lei, Lu, Xu et al. identify cuproptosis as a form of immunogenic cell death that stimulates adaptive antitumour immunity. In turn, CD8⁺ T cell-derived IFNγ enhances tumour sensitivity to cuproptosis through STAT1–IRF1–FDX1 signalling, establishing a reciprocal immunometabolic circuit with important implications for cancer immunotherapy.

The mechanisms by which dietary fructose promotes tumour progression have remained poorly understood. A recent study published in Nature reveals that dietary fructose is metabolized in the liver, resulting in elevated circulating lipid levels that can serve as building blocks for cancer cells outside the liver.

In addition to its physical symptoms, cancer cachexia — a severe wasting syndrome — also leads to fatigue, apathy and depression. A recent study published in Science identifies neural circuit mechanisms that underlie these motivational symptoms.

A recent study published in Nature finds that neuroendocrine small-cell lung cancer (SCLC) cells exhibit electrical activity that directly drives tumour progression and metastasis and shows that they rely on oxidative phosphorylation to meet the high energy demand associated with these electrophysiological processes.

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.

The mechanisms of how pH-dependent cell death, alkaliptosis, is regulated are incompletely understood. Chen et al. now demonstrate that the cholesterol biosynthesis protein CYP51A1 suppresses alkaliptosis induced by the opioid analgesic JTC801.

In this study, Allan Balmain and colleagues used a mouse model to monitor stem cell networks at single-cell resolution during skin carcinogenesis, revealing two cancer stem cell states, rapid cycling and plasticity, between which cells can transition to drive tumour initiation, progression and therapy resistance.

In a recent Nature paper, Ruggero and colleagues found that fasting and ketogenic diets induce metabolic rewiring through a translational mechanism involving MNK-mediated phosphorylation of eIF4E, which enhances ketogenesis. This process creates a metabolic vulnerability in pancreatic cancer that could be therapeutically exploited.

In a recent study published in Cell, Chhabra et al. identify age- and sex-dependent changes in skin fibroblasts that drive melanoma aggressiveness, with aged male fibroblasts promoting a slow-cycling, invasive state and resistance to targeted therapy in melanoma cells.

In a recent study published in Nature, lactate has been identified as a key player in enhancing DNA repair mechanisms in gastric cancer by promoting lactylation of DNA repair proteins, leading to chemotherapy resistance.

In a comprehensive study in acute myeloid leukaemia, Ozga et al. demonstrate sex-specific differences in the frequency and prognostic effect of genetic alterations.