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- 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.
- Authors
McCoach, Caroline E.; Bivona, Trever G.; Blakely, Collin M.; Doebele, Robert C.
- 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.
- Subjects
ANTINEOPLASTIC agents; DRUG therapy; CLINICAL trials; COMBINED modality therapy; DRUG resistance in cancer cells; LUNG cancer; LUNG tumors; RESEARCH funding; TUMOR classification; DISEASE progression; PHARMACODYNAMICS
- Publication
Clinical Lung Cancer, 2016, Vol 17, Issue 5, p466
- ISSN
1525-7304
- Publication type
journal article
- DOI
10.1016/j.cllc.2016.05.025