Issues

Opportunities to accelerate progress against mortality from the leading causes of cancer death were outlined to meet the Cancer Moonshot goal of reducing age-standardized cancer death rates in the United States by 50% by 2047.

Managing concomitant respiratory muscle involvement with mechanical ventilation and treating with abatacept and ruxolitinib may reduce severe immune checkpoint inhibitor myocarditis high fatality rates.

A clinically annotated cohort of 1,031 patients was profiled via whole-exome and RNA sequencing, which characterized novel RNA and DNA markers of refractory metastatic cancer and established the use of this cohort for investigation of resistance mechanisms and predictive analyses.

Quantitative multiplexed microscopy reveals that a subpopulation of cells that coexpress MYC and BCL2 without BCL6 govern clinical outcomes in diffuse large B-cell lymphoma, underscoring the importance of analyzing protein coexpression patterns at single-cell resolution.

Cancer cells reprogrammed into the myeloid lineage adopt an antigen-presenting cell phenotype and function, present endogenous tumor antigens, and stimulate robust antitumor immunity in hematologic malignancies and solid cancers.

T cell-derived cytokines induce apoptosis of MHC-I-deficient tumor cells when TNF signaling and autophagy pathways are targeted, leading to T cell-mediated elimination of tumors with a substantial population of resistant, MHC-I-deficient tumor cells.

The design and testing of a new MDM2-targeted proteolysis-targeting chimera reveals its ability to activate a p73-mediated apoptotic program in p53-mutant or p53-deleted triplenegative breast cancer cells and mouse models while sparing normal cells.

Novel mouse models of cancer-relevant nontetrameric p53 mutants demonstrate that p53 dimers upregulate the PPAR signaling pathway, thus modulating cell metabolism and differentiation ability to confer tumor suppression.

The dimer-forming p53(A347D) mutation has both loss-of-function and gain-of-function properties that drive tumorigenesis and enhance apoptogenic activity, suggesting a potentially targetable therapeutic vulnerability in cancer.