Cancer

Cell culture and mouse studies suggest inhibiting CBLC could help treat EGFR-mutant NSCLC. In two human EGFR-mutant NSCLC cell lines, two shRNAs targeting CBLC decreased viability compared with a non-specific shRNA, and one of the shRNAs plus Iressa gefitinib or Tagrisso osimertinib decreased viability compared with Iressa or Tagrisso alone. In two xenograft mouse models of EGFR-mutant NSCLC, tumor-specific shRNA-mediated knockdown of CBLC decreased tumor size compared with a non-specific shRNA, and tumor-specific CBLC knockdown plus Iressa or Tagrisso decreased tumor size compared with either drug alone. Next steps could include identifying and testing CBLC inhibitors in models of EGFR-mutant lung cancer.

AstraZeneca plc markets Iressa, an EGFR inhibitor, for NSCLC and has the drug in Phase III testing for head and neck cancer and Phase II testing for acute myelogenous leukemia (AML), skin cancer and Cushing’s disease...