Addressing epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer

ABSTRACT

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the survival of patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. However, nearly all EGFR-mutant NSCLC tumors eventually acquire resistance to the currently used EGFR-TKIs and subsequently progress clinically. Acquired resistance to EGFR-TKIs is thus a huge issue in the treatment of EGFR-mutant NSCLC at present. On one hand, T790M second-site mutation has been recognized as a key mechanism of EGFR-TKI resistance, and third generation EGFR-TKIs such as osimertinib and rociletinib have been developed to overcome tumor cells harboring the T790M mutation. On the other hand, combination with cytotoxic chemotherapy is also expected as another strategy for preventing the acquired resistance to current EGFR-TKIs and prolonging the survival benefits by EGFR-TKIs. Here, we review updated strategies for preventing or overcoming acquired resistance to EGFR-TKIs.

KEYWORDS:

• Non-small cell lung cancer
• epidermal growth factor receptor mutation
• epidermal growth factor receptor tyrosine kinase inhibitor
• T790M mutation
• chemotherapy

Declaration of interest

S Kanda reports research funds from AstraZeneca, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.