Researchers at Dana-Farber Cancer Institute have developed a promising new drug candidate, EAI-432, to treat non-small cell lung cancers (NSCLC) driven by mutations in the EGFR gene, particularly the L858R mutation, which is present in about one-third of NSCLC patients. EAI-432, an allosteric inhibitor with high selectivity for the L858R mutation and subsequent clinical resistance mutations, provides a potential new approach for NSCLC patients for whom there are currently no approved targeted therapies. Combination with the current frontline therapy may also lead to enhanced outcomes, delaying the emergence of resistance in that patient population.
Approved EGFR inhibitors bind to the active site of the EGFR target, known as the ATP binding pocket. Unlike other fourth-generation compounds in development, EAI-432, binds to a site separate from the active ATP pocket on EGFR, causing conformational changes and effectively inhibiting it.
