Deciphering the function of oncogenic KRAS has been a central objective in cancer biology. For over four decades, mutations were thought lock KRAS oncoproteins in a constitutive or persistently active state. Piro Litos work has challenged this assumption to reveal new mechanisms leading to the physiologic inactivation of mutant KRAS in cancer cells. In turn, this knowledge has paved the way for the preclinical and clinical development of several approved or emerging KRAS directed therapeutics.

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