The biology and clinical features of non-small cell lung cancers with EML4-ALK translocation.
The anaplastic lymphoma kinase (ALK) acts as a dominant oncogenic driver following chromosomal rearrangements in certain cancers including non-small cell lung cancer (NSCLC). NSCLC with ALK translocation occurs in a specific subset of patients and results in unique clinical features. Crizotinib is a small molecule inhibitor of ALK kinase that has recently been approved by the FDA for the treatment of patients with ALK-positive NSCLC. Treatment with crizotinib results in clinical benefit rate of 85%-90% and a median progression-free survival of 9-10 months for this molecular subset of patients. Ongoing studies will define the impact of crizotinib on overall survival and provide insights into the resistance mechanisms and potential activation of alternate pathways. Heat shock protein 90 inhibitors also appear promising in the treatment of ALK-positive NSCLC patients, based on early results. This article reviews the characteristics, treatment, and ongoing research in patients with ALK-positive NSCLC.
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA. rnpilla@emory.edu
Rathi N
RN
Pillai
Suresh S
SS
Ramalingam
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D002986:Clinical Trials as Topic; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D014178:Translocation, Genetic
C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib