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Vol.56 No.1 contents | Japanese/English |
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- The 30th Lung Cancer Workshop -
Biomarkers for Lung Cancer: Focusing on Targeted Drug Resistance
Seiji Yano11Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Japan
Several driver oncogenes, including EGFR mutations, ALK rearrangement, ROS-1 rearrangement, and RET rearrangement, have been identified in lung adenocarcinoma. EGFR tyrosine kinase inhibitors (TKIs) and ALK-TKIs have been approved for lung cancer with EGFR activating mutations and ALK rearrangements, respectively. In addition, many targeted drugs for other oncogenic drivers are also being evaluated for efficacy in clinical trials. EGFR-TKIs and ALK-TKIs show dramatic therapeutic efficacy against lung cancer with EGFR mutation and ALK rearrangement, respectively. However, the responders almost invariably acquire resistance to EGFR-TKIs within several years. The representative mechanism is a secondary mutation in the target. A new generation of TKIs, which inhibit secondary mutations, has been developed and evaluated for efficacy in clinical trials. Apoptosis resistance is another important mechanism of TKI resistance. BIM polymorphism is associated with EGFR-TKI resistance in EGFR mutant lung cancer. We found that a HDAC inhibitor, vorinostat, could overcome EGFR-TKI resistance associated with BIM polymorphism. According to this observation, we are currently evaluating the safety and efficacy of treatment with EGFR-TKI and vorinostat in an investigator initiated trial (VICTORY-J).
key words: EGFR-TKI, ALK-TKI, Acquired resistance, T790M mutation, BIM polymorphism
JJLC 56 (1): 55-60, 2016
