Search

In a study published in Nature, Lourenço et al. demonstrate that strong oncogenic driver mutations undergo negative selection unless they occur in a permissive tissue context.

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.

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.

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.

Although disulfide stress in cancer cells under glucose starvation is known to trigger disulfidptosis, its role in the tumour microenvironment has remained unclear. A recent study in Nature Cell Biology reveals that in intratumoural CD8⁺ T cells, disulfidptosis promotes T cell exhaustion and thereby limits antitumour imunity.

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.

The 2025 annual meeting of the American Association for Cancer Research (AACR) was held under the theme ‘Unifying Cancer Science and Medicine: A Continuum of Innovation for Impact’. Here, we summarize some key highlights from the meeting.

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 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.

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.

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.

The occurrence of multiple independent tumours in patients with EGFR-mutant lung cancer was unexplained. A recent study in Nature Cancer identified distinct genetic predisposition mechanisms, including developmental mosaicism and germline EGFR variants, that contribute to the formation of multiple primary tumours.

In this study, Alexander et al. find that HIF2α regulates speckle–DNA associations to fine-tune the expression of a subset of its target genes, and demonstrate that speckle phenotypes correlate with outcomes in renal cell carcinoma.

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.

To establish microbiome-based screening for colorectal cancer, a study published in Nature Medicine tackled two key challenges: utilizing quantitative microbiome profiling and identifying covariates that might obscure the microbiota–colorectal cancer interactions.

Wang et al. demonstrate that lactate derived from glioblastoma stem cells, microglia and macrophages drives histone lactylation, activating immunosuppressive transcriptional programs and upregulating CD47, to suppress phagocytosis.

In a recent study published in Nature, Goto et al. explore mechanisms of immune evasion in early colorectal cancers and adenomas and identify SOX17 to be crucial for immune escape through suppression of interferon-γ signalling.

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.

Parreno et al. provide evidence for epigenetically initiated cancers in Drosophila and show that cancer develops after transient loss of Polycomb group proteins in the absence of recurrent mutations.

Goddard et al. report that disseminated tumour cells evade T cell immunity due to their relative scarcity, which decreases the likelihood of T cell–tumour cell interactions.

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

In a recent study, Sanchez-Aguilera, Masmudi-Martín et al. find that a molecular program explains the cognitive impairment often seen in patients with brain metastasis, challenging the prevailing paradigm of the tumour mass being the sole cause of altered brain function.

Maas et al. identify an inflammatory, immunosuppressive phenotype in neutrophils that accumulates in brain malignancies, and show that this tumour-promoting neutrophil activation is driven by the brain tumour microenvironment.

In this study, Bansaccal et al. analyse why, at some skin locations, oncogene-expressing cells rarely progress to cancer and found that a dense dermal collagen network prevents skin cancer formation.

In this study, Weems et al. demonstrate that detachment-induced dynamic blebbing leads to the assembly of pro-survival signalling molecules at the plasma membrane, which protects melanoma cells from anoikis.

In this study, Malladi and colleagues reveal the mechanism by which mitochondrial fragmentation enables latent brain metastatic breast cancer cells to increase fatty acid oxidation to maintain cellular energetics and redox homeostasis.

Sloan and colleagues demonstrate that anthracycline chemotherapy drives metastatic progression by stimulating a cancer cell-mediated increase in nerve fibre activity in the tumour microenvironment, which can be reversed by the use of β-blockers.

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.

This study shows how the selective immune pressure in early-stage tumours drives interferon-γ-dependent metabolic reprogramming in cancer cells to mediate immune escape.

Using single-cell RNA-seq and functional analysis in prostate cancer organoids and mouse models, Chan et al. identify inflammatory JAK–STAT signalling to drive the transition of adenocarcinomas to neuroendocrine prostate cancer.

Ma et al. demonstrate that platelets suppress liver tumour growth in the context of non-alcoholic fatty liver disease through T cell-dependent antitumour immunity.

Two studies published concurrently in Nature report the development and preclinical activity of RMC-7977, a multi-selective inhibitor targeting the active, GTP-bound form of RAS.

Two independent studies published in Nature implicate distal cholesterol biosynthesis in the regulation of ferroptosis and show that 7-dehydrocholesterol (7-DHC) is an endogenous, anti-ferroptotic metabolite.

Ubiquitin ligases (E3s) participate in many cellular processes, including cell cycle progression and cell death. This Review by Senftet al. discusses how deregulation of E3s can lead to tumorigenesis and highlights the opportunities for targeting E3s as an anticancer therapy.

Two independent studies published together in Nature find that AT1 cells can have a role in both the initiation and suppression of lung adenocarcinoma.

Preclinical molecular models are useful that mimic a patient´s response to targeted therapy. Here, the authors establish an in vivo inducible RNAi-mediated gene silencing system in patient-derived xenograft models of acute leukemia to identify individual vulnerabilities and therapeutic targets.

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 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 study, Tagore et al. find that the formation of synapse-like structures that serve to transfer GABA between premalignant melanocytes and keratinocytes promotes melanoma initiation by the BRAF^V600E oncogene.

Altea-Manzano et al. find that factors secreted by primary breast tumours or high-fat diet feeding enriches the fatty acid palmitate in distant organs, which primes pre-metastatic niches enabling metastatic growth.

In this study, Cao et al. identified previously undiscovered metabolites produced by human gut microbes that cause DNA damage, and analysed their implication for colorectal cancer development.

To understand malignant progression, Yuan et al. delineate the complex crosstalk between cancer stem cells and their microenvironment that is initiated by oncogenic RAS.

Karras et al. map cell state diversity in melanoma and identify a cellular hierarchy that is regulated by microenvironmental cues.