Yarden Lab

Weizmann Institute

- · Israel

ERC-funded
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ERC Advanced Grant · 2022

Overcoming Resistance to Anti-cancer Drugs by Blocking Mutation-prone DNA Polymerases and the SOS Response

Background: A large fraction of cancer patients die because their tumors initially respond to drugs but later they evolve tolerance. Thus, resistance to diverse drugs, along with the soaring costs of new treatments, are emerging as major societal issues of the 2020s. Herein, we explore one of the most distressful examples, tolerance of lung cancer to EGFR-specific tyrosine kinase inhibitors (TKIs). Working hypothesis: In similarity to bacteria exposed to antibiotics, when cancer cells are exposed to TKIs they enlist SOS responses, which activate endogenous mutators. Hence, we will combine the relatively effective but mutagenic TKIs with drugs that disarm the mutators. This scheme will be…

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