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ALK inhibitors in non-small cell lung cancer: crizotinib and beyond

Mark M Awad1, Alice T Shaw2

  • 1Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.

Clinical Advances in Hematology & Oncology : H&O
|October 17, 2014
PubMed

Insights

New anaplastic lymphoma kinase (ALK) inhibitors offer improved treatments for advanced non-small cell lung cancer (NSCLC). This review details their properties and challenges in clinical application.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Crizotinib revolutionized anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) treatment.
  • Resistance to crizotinib is a significant clinical challenge.
  • ALK rearrangements are key drivers in a subset of NSCLC.

Purpose of the Study:

  • To review pharmacologic and clinical properties of emerging ALK inhibitors for NSCLC.
  • To discuss challenges in studying and prescribing these novel agents.
  • To explore combination therapies and heat shock protein 90 inhibitors.

Main Methods:

  • Literature review of pharmacologic and clinical data.
  • Analysis of emerging ALK inhibitors, including monotherapies and combinations.
  • Discussion of resistance mechanisms and future therapeutic strategies.

Main Results:

  • Multiple potent ALK inhibitors (e.g., ceritinib, alectinib) are in development.
  • These agents show promise in overcoming crizotinib resistance.
  • Heat shock protein 90 inhibitors represent an alternative therapeutic avenue.

Conclusions:

  • A new generation of ALK inhibitors offers significant therapeutic potential for advanced NSCLC.
  • Careful study design and prescribing strategies are crucial for optimal patient outcomes.
  • Further research into combination therapies and resistance mechanisms is warranted.

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