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Science in Society
Mutations leading to POLE proof-reading deficiency contribute to high tumor burden and predict efficacy of anti–PD-1 therapy in patients with mismatch repair–proficient tumors, suggesting their potential use as a biomarker of cancer immunotherapy response.
Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse
The chromatin repressor PRC2 induces HLA class II silencing in acute myeloid leukemia leading to immune escape and posttransplantation relapse, while its chemical inhibition rescues HLA expression and triggers T cell–mediated leukemia eradication.
Colorectal cancers express abundant viral-like repeat elements that can be targeted by nucleoside reverse transcriptase inhibitors in preclinical models, which was further translated into a phase II clinical trial.
Development and characterization of INCB086550, a potent, selective, and orally bioavailable small-molecule inhibitor of PD-L1, showed antitumor efficacy and represents a new modality to block the PD-L1/PD-1 interaction.
Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C
The structurally unique KRASG12C inhibitor JDQ443 shows potent, mutant-selective antitumor activity in preclinical models as well as in patients, both alone and in combination with the SHP2 inhibitor TNO155.
The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution
Spatial profiling of cutaneous melanoma at the single-cell level provided molecular features of progression and immunosuppression, which include paracrine cytokine signaling and direct immune cell–cell contact.
The REFLECT platform was developed and allows for the identification of targetable coalterations in patient cohorts, with its use in preclinical and clinical settings demonstrating improvements to efficacy and survival.
Type I IFN produced by plasmacytoid dendritic cells in response to histone deacetylase inhibition is required to induce differentiation of leukemia cells and ultimately tumor cell death in acute myeloid leukemia.
Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer
Heterogeneity in the function of carcinoma-associated fibroblasts (CAF) indicated that IL6 depletion from only the αSMA+ CAF subtype led to improvement in gemcitabine response in patients with pancreatic cancer.
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