Brigatinib for ALK-positive metastatic non-small-cell lung cancer: design, development and place in therapy

Drug Des Devel Ther. 2019 Feb 8:13:569-580. doi: 10.2147/DDDT.S147499. eCollection 2019.

Abstract

Despite the benefits of first and second generation anaplastic lymphoma kinase (ALK) inhibitors in the management of ALK-rearranged advanced non-small-cell lung cancer (NSCLC), the development of acquired resistance poses an ongoing dilemma. Brigatinib has demonstrated a wider spectrum of preclinical activity against crizotinib-resistant ALK mutant advanced NSCLC. The current review narrates a brief history of tyrosine kinases, the development and clinical background of brigatinib (including its pharmacology and molecular structure) and its use in ALK-positive NSCLC.

Keywords: ALK inhibitors; ALK positive; TKI; brigatinib; non-small cell lung cancer.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors*
  • Anaplastic Lymphoma Kinase / genetics
  • Anaplastic Lymphoma Kinase / metabolism
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / drug effects
  • Drug Design*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mutation
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*

Substances

  • Antineoplastic Agents
  • Organophosphorus Compounds
  • Pyrimidines
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • brigatinib