Cover ImageDespite significant progress being made to improve cancer mortality in recent years, cancer remains the second leading cause of death in the United States. In 2022, President Biden and First Lady Dr. Biden announced a new Cancer Moonshot goal of reducing age-standardized cancer mortality rates by at least 50% by 2047. In this study, Shiels and colleagues evaluated the trends in cancer mortality from 2000 to 2019 and showed that overall cancer death rates declined by 1.4%/year from 2000 to 2015 and accelerated to 2.3%/year from 2016 to 2019. Analysis of mortality rates of the six most common cancer types showed that recent declines in lung (−4.7%/year, 2014–2019), colorectal (−2.0%/year, 2010–2019), and breast (−1.2%/year, 2013–2019) cancer mortality have contributed to the decline of cancer death rates overall, but trends for pancreatic, prostate, and liver cancers were less promising, suggesting that new strategies to prevent, detect, and treat these and other cancers will be needed to achieve the Moonshot goal. For more information, see the article by Shiels and colleagues on page 1084. Artwork by Bianca Dunn.Close Modal
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In This Issue
In the Spotlight
p53 Oligomerization Domain Mutants: A New Class of Mutants That Retain “License to Kill”
Science in Society
Achieving the Goals of the Cancer Moonshot Requires Progress against All Cancers
A View on Drug Development for Cancer Prevention
Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047
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.
Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Managing concomitant respiratory muscle involvement with mechanical ventilation and treating with abatacept and ruxolitinib may reduce severe immune checkpoint inhibitor myocarditis high fatality rates.
Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer
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.
Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma
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.
Reprogramming Cancer into Antigen-Presenting Cells as a Novel Immunotherapy
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.
Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
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.
Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer
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.
Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program
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.
Li–Fraumeni Syndrome–Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death
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.
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