Multiple cellular pathways can lead to acquired resistance to ALK inhibitors. A common pathway is activation of alternate kinase pathways, including EGFR, KIT, SRC, and IGF1R to maintain activation of downstream ERK and/or PI3K-AKT signaling. Addition of inhibitors to these pathways is a viable response, but not optimal due to the presence of multiple alternatives. Dardaei and co-workers have discovered that SHP2, a nonreceptor tyrosine phosphatase, acts as a common targetable resistance node. Treatment of ALK-resistant patient-derived cells with the selective SHP2 inhibitor, SHP099, combined with an ALK inhibitor restored sensitivity via suppression of ERK1/2 reactivation. Focus Biomolecules has high quality SHP099 in stock at the best price on the market.
