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Cancer Hallmarks Review

Research Briefs

Whole genome and ultra-deep duplex sequencing uncover three different origins of second tumors in children: therapy-related, common, or independent embryologic origin, as well as the mutational impact of chemotherapies in healthy tissues.

Genetic mutations that promote resistance to the EZH2 inhibitor tazemetostat in SMARCB1-deficient epithelioid sarcomas and rhabdoid tumors were identified, and a combination therapy approach to counteract this resistance was proposed, potentially guiding future clinical trials.

Research Articles

Dual KRASG12C/EGFR blockade using adagrasib plus cetuximab shows promising clinical activity and tolerable safety in heavily pretreated patients with KRASG12C-mutated unresectable or metastatic colorectal cancer from the phase I/II KRYSTAL-1 trial.

Broad-spectrum inhibition of RAS-GTP with RMC-6236 is active and tolerated at exposures that induce profound tumor regressions in preclinical models of RAS-driven cancers and that can be associated with objective responses in patients with such cancers.

Distinct microenvironment architectures and spatial cellular niches were observed in earlystage non–small cell lung cancer and were linked to tumor immunogenicity, metabolism, and clonal evolution, implicating neutrophils in poor patient outcomes.

Change in cell-free DNA methylomes and fragmentomes after just two cycles of pembrolizumab were associated with progression-free and overall survival in patients with various metastatic cancers, without requiring matched tumor tissue.

A deep learning model trained on genomic data from routine clinical sequencing accurately classifies 38 distinct tumor types, enabling guided treatment decisions for patients with cancers of unknown or uncertain origin.

A high-quality single-cell chromatin accessibility atlas of colorectal cancer epithelial cells identified two epigenetic subgroups that match intrinsic-consensus molecular subtypes along with key transcription factors and their synergistic modules that regulate subtype-specific phenotypic features.

Multi-modal analysis of tumor-infiltrating lymphocytes in glioblastoma (GBM) revealed a lack of canonically exhausted CD8+ T cells and an enrichment of clonally expanded GZMK-expressing CD8+ T cells, which may have implications for immunotherapy in GBM.

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