Diagnosis and Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

Hematol Oncol Clin North Am. 2017 Feb;31(1):101-111. doi: 10.1016/j.hoc.2016.08.012.

Abstract

Anaplastic lymphoma kinase (ALK) gene rearrangements occur in a small portion of patients with non-small cell lung cancer (NSCLC). These gene rearrangements lead to constitutive activation of the ALK kinase and subsequent ALK-driven tumor formation. Patients with tumors harboring such rearrangements are highly sensitive to ALK inhibitors, such as crizotinib, ceritinib, and alectinib. Resistance to these kinase inhibitors occurs through several mechanisms, resulting in ongoing clinical challenges. This review summarizes the biology of ALK-positive lung cancer, methods for diagnosing ALK-positive NSCLC, current FDA-approved ALK inhibitors, mechanisms of resistance to ALK inhibition, and potential strategies to combat resistance.

Keywords: Alectinib; Anaplastic lymphoma kinase inhibitors (ALK inhibitors); Ceritinb; Crizotinib; EML4-ALK rearrangement; Non–small cell lung cancer (NSCLC).

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Carbazoles / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / enzymology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Crizotinib
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / enzymology
  • Lung Neoplasms* / genetics
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Pyrimidines / therapeutic use
  • Receptor Protein-Tyrosine Kinases* / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases* / genetics
  • Receptor Protein-Tyrosine Kinases* / metabolism
  • Sulfones / therapeutic use

Substances

  • Carbazoles
  • Neoplasm Proteins
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • Sulfones
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • ceritinib
  • alectinib