Identification of Existing Drugs That Effectively Target NTRK1 and ROS1 Rearrangements in Lung Cancer.

ABSTRACT:

Purpose

Efforts to discover drugs that overcome resistance to targeted therapies in patients with rare oncogenic alterations, such as NTRK1 and ROS1 rearrangements, are complicated by the cost and protracted timeline of drug discovery.

Experimental design

In an effort to identify inhibitors of NTRK1 and ROS1, which are aberrantly activated in some patients with non-small cell lung cancer (NSCLC), we created and screened a library of existing targeted drugs against Ba/F3 cells transformed with these oncogenes.

Results

This screen identified the FDA-approved drug cabozantinib as a potent inhibitor of CD74-ROS1-transformed Ba/F3, including the crizotinib-resistant mutants G2032R and L2026M (IC₅₀ = 9, 26, and 11 nmol/L, respectively). Cabozantinib inhibited CD7

SUBMITTER: Chong CR 

PROVIDER: S-EPMC5203969 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature