Potential mechanisms of resistance to ALK inhibitors

The Broad Institute did research on various types of resistance that can form to ALK inhibitors and published the results in Cell.

“Understanding of the mechanisms leading to drug resistance is essential for the design of therapeutic strategies to improve efficacy. Here, we present findings from a systematic large-scale functional study of resistance to ALK inhibition in ALK-rearranged lung cancer. At least 10 of the 54 ORFs [genes] identified as potential drivers of resistance to ALK inhibition represent pathways and proteins previously implicated in clinical resistance to targeted therapies in lung cancer.”

“In total, approximately half of the resistance drivers identified from our study reactivate MEK/ERK and/or PI3K signaling”

“Our findings nominate several possible agents (including inhibitors of EGFR, HER2/HER3, or PKC) that might, in principle, be combined with ALK inhibition to overcome or delay a range of resistance mechanisms.”


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