Volume 2 Issue 10, October 2021

Shedding light on epigenetic mechanisms controlling anti-tumor immune responses, a new study shows that the tumor-intrinsic ring finger protein 2 (RNF2), the catalytic subunit of Polycomb repressor complex 1 (PRC1), acts as a negative regulator of a collaborative NK and CD4⁺ T cell anti-tumor immune response against breast cancer.

Clinical interpretation of cancer genomes for therapy selection and clinical hypothesis generation is an urgent and complex endeavor. A new study brings together a diverse set of data sources to automatically prioritize first- and second-order genomic alterations to provide a meaningful set of interpretations based on a patient’s molecular profile.

DNA methyltransferase inhibitors are widely used in preclinical and clinical studies, but poor pharmacokinetics and low efficacy in solid tumors limit their therapeutic use. A new study reports the development and characterization of a specific, non-covalent DNA methyltransferase inhibitor with more-durable DNA hypomethylation and lower toxicity than that of nucleoside analogs.

Pappalardi and colleagues identify a potent noncovalent DNMT1-selective inhibitor with improved tolerability and efficacy in preclinical AML models compared with clinically validated covalent pan-DNMT inhibitors.

Using in vivo models and human cancer datasets, Yang and colleagues identify a role for the epigenetic regulator Rnf2 in repressing the antitumor immune responses of natural killer and CD4⁺ T cells.

Mizukoshi and colleagues use patient samples and xenotransplants to show that the microbiota associated with chronic liver disease promote liver carcinogenesis through gelE-positive Enterococcus faecalis via induction of TLR4–Myd88 signaling.

Straussman and colleagues undertake clonal analyses and show that drug tolerance to EGFR therapy in lung cancer cell populations is an inherited continuous trait that is determined by IRS1 phosphorylation.

Jacks and colleagues demonstrate the effects of neoantigen expression level on T-cell priming and immune surveillance during tumor development and progression and explore implications for immunotherapies, using in vivo models of colorectal cancer.

Klemm et al. show that resistance to CSF1R inhibition in breast cancer brain metastasis is driven by compensatory activation of the CSF2Rb–STAT5 axis in macrophages, which can be alleviated by combined targeting of CSF1R and STAT5.

Van Allen and colleagues develop a data-integration framework with an underlying knowledge base supporting clinical decision making and also serving as a hypothesis-generating platform, which the authors benchmark and validate across several retrospective cohorts and a prospective precision oncology trial.