Cancer Grand Challenges is a unique funding platform that dares global, multidisciplinary teams of researchers to come together, think differently, and tackle some of the toughest challenges in cancer research. Here, we discuss the nine intractable challenges currently open for application.
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| http://dx.doi.org/10.1158/2159-8290.CD-20-1657 | DOI Listing |
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ZNFX1 functions as a master regulator of epigenetically induced pathogen mimicry and inflammasome signaling in cancer.
Cancer Res
January 2025
University of Maryland, Baltimore, Baltimore, Maryland, United States.
DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.
View Article and Find Full Text PDFCancer Research in the Age of Spatial Omics: Lessons from IMAXT.
Cancer Discov
January 2025
CRUK Cambridge Institute, University of Cambridge. Li Ka Shing Centre, Cambridge, United Kingdom.
The Imaging and Molecular Annotation of Xenografts and Tumors Cancer Grand Challenges team was set up with the objective of developing the "next generation" of pathology and cancer research by using a combination of single-cell and spatial omics tools to produce 3D molecularly annotated maps of tumors. Its activities overlapped, and in some cases catalyzed, a spatial revolution in biology that saw new technologies being deployed to investigate the roles of tumor heterogeneity and of the tumor micro-environment. See related article by Stratton et al.
View Article and Find Full Text PDFConquering Overtreatment of DCIS: Lessons from PRECISION.
Cancer Discov
January 2025
Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment. See related article by Bressan et al.
View Article and Find Full Text PDFImplementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs.
Cancer Discov
January 2025
Department of Analytical, Environmental and Forensic Sciences, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom.
The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases. See related article by Bressan et al.
View Article and Find Full Text PDFVisualizing Cancer Heterogeneity at the Molecular and Cellular Levels: Lessons from Rosetta.
Cancer Discov
January 2025
Bioscience, Early Oncology, AstraZeneca, Cambridge, United Kingdom.
Understanding tumor heterogeneity is a major challenge that was recognized as one of the first Cancer Grand Challenges, with a call to provide solutions to visualize tumor heterogeneity. The Rosetta team took on this challenge, exploiting advances in spatial-omics approaches centered around mass spectrometry imaging to map tumor heterogeneity at the cellular and molecular scales with different levels of resolution. See related article by Bressan et al.
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