Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy

The biggest hurdle to targeted cancer therapy is the inevitable emergence of drug resistance. Tumor cells employ different mechanisms to resist the targeting agent. Most commonly in EGFR-mutant non-small cell lung cancer, secondary resistance mutations on the target kinase domain emerge to diminish the binding affinity of first- and second-generation inhibitors. Other alternative resistance mechanisms include activating complementary bypass pathways and phenotypic transformation. Sequential monotherapies promise to temporarily address the problem of acquired drug resistance, but evidently are limited by the tumor cells' ability to adapt and evolve new resistance mechanisms to persist in the drug environment.…

• UO
  University of Pennsylvania
• PS
  Pennsylvania State University
• WV
  West Virginia University
• CI
  Cancer Institute, West Virginia University
• PS
  Penn State Hershey Cancer Institute