Escaping ALK inhibition: mechanisms of and strategies to overcome resistance.
Mutated anaplastic lymphoma kinase (ALK) drives the development of multiple tumor types, and ALK tyrosine kinase inhibitors such as crizotinib have been validated as targeted therapeutics. Unfortunately, as with other oncogene-driven tumors, therapeutic resistance invariably develops. In Science Translational Medicine, two recent studies provide new insight into mechanisms of resistance to ALK tyrosine kinase inhibitors and possible strategies to overcome this resistance.
Department of Medicine, Division of Hematology and Oncology, Vanderbilt University, Nashville, TN 37232, USA.
Christine M
CM
Lovly
William
W
Pao
D000077548:Anaplastic Lymphoma Kinase; D000077547:Crizotinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases