Research ArticleCancer

Targeting p53-dependent stem cell loss for intestinal chemoprotection

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Science Translational Medicine  07 Feb 2018:
Vol. 10, Issue 427, eaam7610
DOI: 10.1126/scitranslmed.aam7610

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Safer without PUMA

Gastrointestinal toxicity is a major cause of side effects from chemotherapy and radiation, which can greatly decrease the quality of life and limit the dosing of cancer treatments. Tumor suppressor p53 plays a major role in chemotherapy-induced intestinal cell death, but inhibiting p53 is not safe because a loss of p53 would worsen cancer growth. Instead, Leibowitz et al. showed that one can block only the detrimental function of p53 by inhibiting its downstream effector, PUMA. A small-molecule inhibitor of PUMA protected intestinal cells in mice and in human colon organoids but did not protect cancer cells, suggesting that this could be a viable strategy for intestinal protection in cancer patients.