Resistance to molecularly targeted therapy in non-small-cell lung cancer

Respir Investig. 2019 Jan;57(1):20-26. doi: 10.1016/j.resinv.2018.09.001. Epub 2018 Oct 4.

Abstract

The discovery of oncogenic driver gene mutations, including epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, and ret proto-oncogene (RET) fusion, has led to the development of molecularly targeted therapy for non-small-cell lung cancer (NSCLC). This therapy has changed the standard of care for NSCLC. Despite the dramatic response to molecularly targeted therapy, almost all patients ultimately develop resistance to the drugs. To understand the mechanisms of resistance to molecularly targeted agents, it is essential to understand the molecular pathways of NSCLC. Here, we review the mechanisms of resistance to molecularly targeted therapy and discuss strategies to overcome drug resistance.

Keywords: ALK; Acquired resistance; EGFR; Lung cancer; Molecularly targeted therapy.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Epidermal Growth Factor / genetics
  • Gene Fusion
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / therapy*
  • Molecular Targeted Therapy*
  • Mutation
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret / genetics

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Epidermal Growth Factor
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • ROS1 protein, human