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Shooting the dark side of cancer’s “moon”

November 7, 2022

Fifty-three years after U.S. astronauts became the first humans to walk on the moon, VICC researchers are participating in an equally audacious adventure—a “Cancer Moonshot” aimed at cracking the conundrum of colorectal cancer.

Funded through the $1.8 billion 21st Century Cures Act passed by Congress in 2016, the National Cancer Institute’s Cancer Moonshot Initiative has recruited investigators across the country to construct three-dimensional atlases of the dynamic cellular, morphological and molecular features of human cancers as they evolve from precancerous lesions to advanced disease. 

Vanderbilt’s role in the initiative is COLON MAP, the Colorectal Molecular Atlas Project, part of the Human Tumor Atlas Network. Led by Robert Coffey, MD, Ken Lau, PhD, and Martha Shrubsole, PhD, COLON MAP is supported by a five-year, $11 

million Moonshot grant awarded in 2018. This grant is a direct outgrowth of the GI SPORE work.

By mapping the routes that benign colonic polyps take to progress to malignancy, the researchers hope to identify those at greatest risk for colorectal cancer and to discover cell characteristics that could lead to novel chemoprevention strategies.

The program begins by collecting polyp tissue from a diverse group of participants who are undergoing colonoscopies or surgical resections of large polyps at Vanderbilt University Medical Center. Sophisticated techniques including single-cell RNA sequencing, multiplex immunofluorescence and multiplex immunohistochemistry are used to evaluate the samples.

Two distinct pathways to colorectal cancer have been identified: conventional adenomas and sessile serrated polyps. 

Last year the COLON MAP investigators reported that conventional adenomas arise from the expansion of stem cells driven by activation of the WNT signaling pathway and associated regenerative programs, while serrated cells activate gene networks related to damage response and metaplasia. Serrated polyps also are infiltrated by cytotoxic immune cells.

Shrubsole, research professor of Medicine (Epidemiology), was invited in June to give an update on the research at a joint virtual meeting of the NCI Board of Scientific Advisors and National Cancer Advisory Board.