Exciting new targets in lung cancer therapy: ALK, IGF-1R, HDAC, and Hh.
The anaplastic lymphoma kinase (ALK) inhibitor crizotinib will become an integral addition to the treatment of patients with non-small cell lung cancer (NSCLC) harboring genetic ALK translocations. The insulin-like growth factor receptor (IGF-1R) monoclonal antibody figitumumab, while initially promising, appears to increase toxicity and death in combination with chemotherapy in the treatment of patients with NSCLC of squamous histology; therefore, clinical development of this class of agents will need to proceed with caution. The histone deacetylation (HDAC) inhibitor vorinostat did not demonstrate an improvement in overall survival (OS) compared with placebo in a large randomized trial, but other agents in this class may have greater selectivity and efficacy. Inhibitors of the hedgehog (Hh) signaling pathways have some early clinical promise in both NSCLC and small cell lung cancer (SCLC), and larger studies using these agents are eagerly anticipated.
Neal
Joel W
JW
Stanford Cancer Center, 875 Blake Wilbur Drive, Stanford, CA 94305, USA, jwneal@stanford.edu
Sequist
Lecia V
LV
D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D056572:Histone Deacetylase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D006655:Histone Deacetylases