In This Issue
In the Spotlight
Overcoming PD-1 Blockade Resistance with CpG-A Toll-Like Receptor 9 Agonist Vidutolimod in Patients with Metastatic Melanoma
Intratumoral vidutolimod (CpG-A TLR9 agonist) together with pembrolizumab overcomes PD-1 blockade resistance in 25% of patients with metastatic melanoma with manageable toxicities in a phase I trial.
Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing
Analysis of data from the Genomes for Kids research study reveals the value of three-platform whole-genome, wholeexome, and RNA sequencing in identifying clinically and biologically relevant lesions in pediatric cancer.
Longitudinal Single-Cell Dynamics of Chromatin Accessibility and Mitochondrial Mutations in Chronic Lymphocytic Leukemia Mirror Disease History
AKT Degradation Selectively Inhibits the Growth of PI3K/PTEN Pathway–Mutant Cancers with Wild-Type KRAS and BRAF by Destabilizing Aurora Kinase B
AKT depletion using a degrader proved superior to kinase inhibition due to sustained repression of AKT signaling and destabilization of AURKB, leading to induction of G2/M arrest, hyperploidy, and cell death.
Pharmacologic Activation of p53 Triggers Viral Mimicry Response Thereby Abolishing Tumor Immune Evasion and Promoting Antitumor Immunity
Reactivation of p53 by MDM2 inhibitors potentiates anticancer immune surveillance through derepression of ERVs and dsRNA stress, resulting in induction of the interferon pathway and improved response to checkpoint therapy.
A Humanized Animal Model Predicts Clonal Evolution and Therapeutic Vulnerabilities in Myeloproliferative Neoplasms
Tumor Microenvironment–Derived R-spondins Enhance Antitumor Immunity to Suppress Tumor Growth and Sensitize for Immune Checkpoint Blockade Therapy
Genetic screening in a mouse model of biliary cancer revealed Pik3caH1047R activation but not oncogenic KrasG12D as critical for transformation and tumor formation and additionally reveals the context- and tissue-specific nature of oncogenic drivers.
Blocking Short-Form Ron Eliminates Breast Cancer Metastases through Accumulation of Stem-Like CD4+ T Cells That Subvert Immunosuppression
Inhibition of a specific isoform of RON receptor tyrosine kinase (SF-RON) recruits stemlike CD4 T cells to the metastatic site and promotes strong antitumor immune responses that severely restrict growth of breast cancer metastases.
Oncogenic NPM1c mutations prime acute myeloid leukemia cells for mitochondrial targeting by actinomycin D, which restores PML nuclear bodies—driven senescence and is synergistic with venetoclax to induce tumor clearance.
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