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Mesothelioma is a highly lethal cancer that remains challenging to diagnose. Here, the authors curate a histomorphological atlas of resected mesothelioma and map it using self-supervised AI endorsed by human pathological assessment, revealing patterns that generate highly interpretable predictions.

Human papillomavirus (HPV)-associated oropharyngeal cancer is increasing but the natural history of oral HPV infection is not well understood. Here, the authors investigate clearance of oncogenic oral HPV infection in a cohort of men from the US, Brazil, and Mexico.

In the randomized phase 3 AMPLITUDE trial, patients with HRR-deficient mCSPC experienced longer progression-free survival when they were treated with niraparib and AAP compared to placebo and AAP.

This prespecified updated survival and exploratory subgroup efficacy analysis of the phase 3 DESTINY-Breast04 trial shows that trastuzumab deruxtecan treatment in patients with HER2-low metastatic breast cancer leads to continuous survival benefit irrespective of estrogen receptor or hormone receptor status.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

The authors present a molecular classification of acute leukemia using 5-methylcytosine signatures, together with a neural network-based classifier for clinical use.

A combination of mouse model data and data from a randomized phase 2 trial in patients with breast cancer in remission demonstrates feasibility, safety and a reduction in residual tumor cells following treatment with hydroxychloroquine and/or everolimus.

The location of EGFR exon 20 loop insertions (EGFRex20ins) has been shown to alter sensitivity to lung cancer therapy. Here, the authors report the results of the ZENITH20 clinical trial investigating poziotinib (EGFR TKI) in lung cancer patients and, combining with a similar trial, investigate how structural differences due to location of EGGFRex20ins alters sensitivity to EGFR TKI.

Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.

The function and regulatory mechanism of mRNA acetylation modification in cancer progression remains largely unknown. Here the authors identify that targeting tumor N4-acetylcytidine (ac4C) RNA acetyltransferase NAT10 improves anti-tumor response via MYC/CDK2/DNMT1/dsRNA/type I IFN pathway, and show the synergic anti-tumor effect of NAT10 inhibition with aPD-1.

Glioblastoma therapy is challenging, and new approaches are needed. Here, the authors report on a mitochondrial targeting nanomotor with self-feedback mechanisms to trigger the mineralisation of mitochondria which together with curcumin, inhibits glioblastoma progression.

Metronomic photodynamic therapy is a long-term, low-dose treatment strategy limited by the need of continuous photosensitizer administration. Here this group reports combining the self-bioluminescent bacteria with a neutral red photosensitizer in alginate microcapsules as a self-driven metronomic photodynamic therapeutic system with preclinical anti-cancer effects.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

Mark Samuels and colleagues report the identification of mutations in ORC4, which encodes a component of the origin recognition complex, in individuals with Meier-Gorlin syndrome. The features of this syndrome include small stature, small external ears and small or absent patellae.

In the CheckMate 142 study, nivolumab (anti-PD-1) alone and in combination with ipilimumab (anti-CTLA-4) was shown to induce durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Here, the authors perform exploratory biomarker analysis of the CheckMate 142 study.

Current prognostic biomarkers for colorectal cancer (CRC) tend to lack generalisability across different cohorts and platforms. Here, the authors introduce PIANOS, a classifier for stratifying CRC patients into distinct risk groups across different platforms and cohorts, which allows predicting clinical outcomes and therapies.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

Five-year follow-up and prespecified exploratory biomarker analysis from the phase 3 KEYNOTE-426 trial show that pembrolizumab plus axitinib compared to sunitinib as first-line therapy continues to show overall and progression-free survival benefits in patients with advanced clear cell renal cell carcinoma and indicate that a T-cell-inflamed gene expression profile is predictive of response.

Vallentgoed et al. integrate clinical and multiomic data from persons with matched initial and recurrent IDH-mutant astrocytomas to identify progression-associated mechanisms and report a DNA methylation-based signature associated with survival.

High IL1RL1 correlates with poor survival in acute myeloid leukemia. A stress-driven IL-33/IL1RL1 loop induces leukemogenesis and a tolerogenic immune environment. Targeting this axis with bispecific antibodies offers a promising treatment.

Chemotherapy is commonly used for the treatment of cancer but resistance often occurs. Here, the authors identify mitochondrial DLAT as driver of chemotherapy resistance via interaction with (MTHFD2) and develop a decoy peptide which blocks this interaction, restoring sensitivity to chemotherapy.

In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.

This large integrated analysis of the KRAS^G12C inhibitor sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 trials shows that low expression of TTF-1 and high expression of NRF2 determine anti-tumor efficacy of sotorasib in non–small-cell lung cancer.

In cohort B of the phase 2 SWOG S1512 trial, pembrolizumab monotherapy in patients with unresectable desmoplastic melanoma elicited a complete response rate of 37% and an objective response rate of 89%, supporting a new treatment option for this tumor type.

Huang et al. analyzed serial samples from participants with metastatic non-small cell lung cancer treated with radiotherapy followed by immunotherapy and report improved clinical outcomes and enhanced antitumor responses in immunologically cold tumors.

In the secondary endpoint analysis of the phase 3 SONIA trial, circulating tumor DNA (ctDNA) analysis showed that a pretreatment aneuploidy-based high ctDNA level in patients with advanced breast cancer was associated with benefit from first-line treatment with CDK4/6 inhibitors.

In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

This study explores the genomic and transcriptomic landscapes of triple-negative breast cancer in African American women. The authors show that the mutational profile is broadly similar to that observed in European and East Asian ancestry women while highlighting some interesting differences.

Circulating tumor cell (CTC) clusters are much more likely to produce viable metastasis than single CTCs. Here the authors find that the transmembrane protein Plexin-B2 (PLXNB2) mediates homotypic and heterotypic CTC cluster formation, driving lung metastasis in breast cancer mouse models.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

The natural progression of tumours and their treatment can influence tumour evolution. Here, authors analyse whole-exome sequencing data from various cancer cohorts, finding that treatment-resistant tumors shift toward neutral evolution, which correlates with worse prognosis, and monitoring this shift may guide treatment decisions.

Gain-of-function mutations in CTNNB1 (encoding for b-catenin) leading to deregulated Wnt/β-catenin signaling are frequently observed in patients with hepatocellular carcinoma (HCC). Here the authors show that inhibiting b-catenin with lipid nanoparticles encapsulating siRNA targeting CTNNB1 impairs tumor growth and promotes anti-tumor immunity in preclinical HCC models.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

Cellular niches are highly heterogenous in triple negative breast cancer. Here, the authors utilise imaging mass cytometry and spatial transcriptomics to characterise the microenvironment in Black American and White American patients.

Bruton tyrosine kinase (BTK) inhibitors can interrupt the crosstalk between follicular lymphoma FL cells and macrophages thereby inducing downregulation of pro-survival pathways in FL cells. Here this group reports a phase 2 single-arm trial evaluating the regimen of acalabrutinib with lenalidomide plus rituximab on twenty four patients with previously untreated FL.

Comprehensive pan-cancer analysis of loss of the Y chromosome (LOY) in benign and malignant cells establishes a new model linking LOY in circulating and tumour-infiltrating immune cells to LOY in malignant cells.

Li et al. characterize overlapping and divergent metabolic requirements of human and murine NK cells in response to activation, with a focus on serine metabolism

Wang et al. designed sphingomyelin-derived vesicles that deliver paclitaxel to tumor site, improving its therapeutic efficacy and reducing associated toxicities, in mouse models of breast and pancreatic cancers.

Currently, the biological and clinical implications of copy number alteration (CNA) size heterogeneity and co-occurrence are incompletely understood. Here, the authors use 691 meningiomas and 29 cancer types from The Cancer Genome Atlas to develop size-dependent CNA and CNA co-occurrence models to optimize individualized pan-cancer risk stratification.

Checkpoint inhibitor (CPI) therapy is modestly effective in Glioblastoma patients, with some patients not benefitting at all. Authors here present the outcomes of single arm prospective clinical trial employing combination CPI therapy in newly diagnosed GBM and identify the pre-treatment genetic, microbiome and immunological factors that might contribute to sensitivity.

Early breast cancer is often responsive to treatment, however, long-term prognosis is variable. Here, the authors utilise a deep learning model to predict metastasis free survival using digitised tumour slides.

A modular anti-albumin nanobody conjugated to a STING agonist enhances antitumour immunity by improving pharmacokinetics, tumour accumulation and immune responses, inhibiting murine tumour growth and enhancing cancer immunotherapies.

Axonal injury, induced in the white matter by expansion of early tumour cells, is a key driver of glioblastoma progression.