What is it about?

For decades, scientists have been looking for ways to circumvent resistance of cancer cells to therapy. In this study, we utilized CRISPR metabolic screen to identify genes of resistance to inhibitors of DNA repair kinase ATM. We discovered that a gene called KEAP1 is particularly required for invasive breast and lung cancer cells to survive upon ATM kinase inhibition.

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Why is it important?

Our study provides strong evidence supporting the stratification of patients with KEAP1-mutants tumors as likely responders to ATM inhibitors.


This study has led to the identification of an unprecedented synthetic lethality between inhibition of the DNA repair response kinase ATM and deficiency in KEAP1, a master regulator of redox homeostasis in mammalian cells. We hope this study will enhance our ability to establish a new strategy for cancer precision medicine, particularly for patients with triple negative breast cancer and non small cell lung cancer.

Urbain Weyemi
National Cancer Institute

Read the Original

This page is a summary of: CRISPR metabolic screen identifies ATM and KEAP1 as targetable genetic vulnerabilities in solid tumors, Proceedings of the National Academy of Sciences, February 2023, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2212072120.
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