ALK: a tyrosine kinase target for cancer therapy
- Vijaykumar R. Holla1,
- Yasir Y. Elamin2,
- Ann Marie Bailey1,
- Amber M. Johnson1,
- Beate C. Litzenburger1,
- Yekaterina B. Khotskaya1,
- Nora S. Sanchez1,
- Jia Zeng1,
- Md Abu Shufean1,
- Kenna R. Shaw1,
- John Mendelsohn1,3,
- Gordon B. Mills1,4,
- Funda Meric-Bernstam1,5,6 and
- George R. Simon2
- 1Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 2Department of Thoracic/Head and Neck, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 3Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 4Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 5Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 6Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
- Corresponding author: gsimon{at}mdanderson.org
Abstract
The anaplastic lymphoma kinase (ALK) gene plays an important physiologic role in the development of the brain and can be oncogenically altered in several malignancies, including non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphomas (ALCL). Most prevalent ALK alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, ALK copy-number gains and activating ALK mutations have been described. Dramatic and often prolonged responses are seen in patients with ALK alterations when treated with ALK inhibitors. Three of these—crizotinib, ceritinib, and alectinib—are now FDA approved for the treatment of metastatic NSCLC positive for ALK fusions. However, the emergence of resistance is universal. Newer ALK inhibitors and other targeting strategies are being developed to counteract the newly emergent mechanism(s) of ALK inhibitor resistance. This review outlines the recent developments in our understanding and treatment of tumors with ALK alterations.
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