title: HSP90 inhibitors in lung cancer: promise still unfulfilled.
abstract: Despite recent advances in the treatment of lung cancer, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths in the United States and worldwide, with a 5-year survival rate of less than 17%. Analysis of the molecular drivers of NSCLC led to the recognition that NSCLC is a collection of distinct, molecularly driven neoplasms. Several subsets of NSCLC with clinical relevance to targeted therapies are defined based on alterations in EGFR, ALK, and other key oncogenic drivers. However, for many oncogenic drivers-such as mutant KRAS-targeted therapies are lacking. Heat shock protein 90 (HSP90) is an adenosine triphosphate (ATP)-dependent molecular chaperone that is critically required for the stability of its clientele, many of which are driver oncoproteins. Therefore, HSP90 inhibitors could prove to be an effective and alternate approach to treat patients with NSCLC that has a specific molecular background or that has acquired resistance to other drugs. Over the last 2 decades, several HSP90 inhibitors have been developed that produced promising preclinical and clinical results. The quest is far from over, however. In this review, we discuss the development and the preclinical and clinical profiles of some of the HSP90 inhibitors that may help to improve the targeted treatment of NSCLC.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Suman
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Saveri
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Burns
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002986:Clinical Trials as Topic; D004260:DNA Repair; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; C117307:KRAS protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras)