Forest White and Cameron Flower PhD ’24 have uncovered why drugs that inhibit tyrosine kinase signaling pathways, such as imatinib (Gleevec), fail in some patients. By analyzing tumor phosphoproteomics, the White Lab team found that many resistant cells are intrinsically wired to resist tyrosine kinase inhibitors: backup signaling networks are already running to support vital functions such as cell growth and division, even when tyrosine kinase inhibitors work as intended.
As reported in Proceedings of the National Academy of Sciences, researchers overcame this resistance in cell models by pairing a tyrosine kinase inhibitor with a drug that targets the backup pathway—an approach currently in clinical trials for lung cancer.
“We are really excited to watch these clinical trials and to see how well patients do on these combinations. And I really think there’s a future for using tyrosine phosphoproteomics to guide this clinical decision-making,” White says. The research was funded in part by the MIT Center for Precision Cancer Medicine.