title: Neoadjuvant Oncogene-Targeted Therapy in Early Stage Non-Small-Cell Lung Cancer as a Strategy to Improve Clinical Outcome and Identify Early Mechanisms of Resistance.
abstract: Evaluations of resistance mechanisms to targeted treatments in non-small-cell lung cancer (NSCLC) are necessary for development of improved treatment after disease progression and to help delay progression of disease. Populations of cells that survive after initial treatment form the basis of resistance via outgrowth of resistant clones or activation of alternative signaling pathways. In this report we describe a clinical trial approach in which patients with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), C-ros-1 proto-oncogene (ROS1), and hepatocyte growth factor receptor (MET) exon 14 alterations and early stage (IA-IIIA) NSCLC will be treated with induction EGFR tyrosine kinase inhibitor (TKI) or crizotinib, a TKI that inhibits ALK, ROS1, and MET. We will evaluate resected tumor samples for pathologic response to induction therapy, overall response rate, and disease-free survival. Additionally, we will assess patients for early evidence of resistance to targeted therapy in terms of activation of alternative signaling pathways and for identification of resistance clones in remnant cell populations.
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado, Denver, Aurora, CO. Electronic address: Caroline.McCoach@ucdenver.edu.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: McCoach
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA.
authors.forename: Trever G
authors.initials: TG
authors.lastname: Bivona
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.
authors.forename: Collin M
authors.initials: CM
authors.lastname: Blakely
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado, Denver, Aurora, CO.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Doebele
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic / Q000379:methods; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D000090063:Proto-Oncogene Mas
chemical_list: D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas
keywords: ALK; Acquired resistance; Clinical trial; Crizotinib; EGFR; MET exon 14; NSCLC; Neoadjuvant treatment; ROS1