SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy.

Alexander E Drilon Manish R Sharma Melissa Lynne Johnson Timothy Anthony Yap Shirish M Gadgeel Dale Nepert Gang Feng Micaela B Reddy Allison S Harney Mohamed S A Elsayed Adam W Cook Christina E Wong Ronald J Hinklin Yutong Jiang Eric N Brown Nickolas A Neitzel Ellen R Laird Wen-I Wu Anurag Singh Ping Wei Keith A Ching John J Gaudino Patrice A Lee Dylan P Hartley S Michael Rothenberg

Published in: Cancer discovery (2023)

PF-07284892-targeted therapy combinations overcame bypass-signaling-mediated resistance in a clinical setting in which neither component was active on its own. This provides proof of concept of the utility of SHP2 inhibitors in overcoming resistance to diverse targeted therapies and provides a paradigm for accelerated testing of novel drug combinations early in clinical development. See related commentary by Hernando-Calvo and Garralda.

Keyphrases

combination therapy