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

Robert Ali1, Junaid Arshad1, Sofia Palacio1

  • 1Department of Medicine, Division of Oncology, Jackson Memorial Hospital, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Centre, Miami, FL 33131, USA, robert.ali@jhsmiami.org.

Drug Design, Development and Therapy
|February 27, 2019
PubMed

Insights

Brigatinib shows promise in treating advanced non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangements, even when resistance to other ALK inhibitors develops. This review covers brigatinib

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Anaplastic lymphoma kinase (ALK) inhibitors are crucial for advanced non-small-cell lung cancer (NSCLC).
  • Acquired resistance to first and second-generation ALK inhibitors presents a significant clinical challenge.
  • Brigatinib exhibits preclinical efficacy against ALK-mutant NSCLC resistant to crizotinib.

Purpose of the Study:

  • To review the history of tyrosine kinases.
  • To detail the development, pharmacology, and molecular structure of brigatinib.
  • To discuss the clinical application of brigatinib in ALK-positive NSCLC.

Main Methods:

  • Literature review of tyrosine kinase inhibitors.
  • Analysis of preclinical data for brigatinib.
  • Review of clinical studies and background information on brigatinib.

Main Results:

  • Brigatinib demonstrates broad preclinical activity against various ALK mutations.
  • Brigatinib overcomes resistance mechanisms developed against earlier ALK inhibitors.
  • Brigatinib's pharmacology and molecular structure support its efficacy.

Conclusions:

  • Brigatinib represents a potential therapeutic option for patients with advanced ALK-positive NSCLC who have developed resistance.
  • Further clinical investigation of brigatinib is warranted for this patient population.
Keywords:
ALK inhibitorsALK positiveTKIbrigatinibnon-small cell lung cancer

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