Main Research Focus
Dr. Doebele’s research is focused on basic and translational research related to lung cancer. His laboratory is developing predictive biomarkers for targeted lung cancer therapy and studying the molecular mechanisms of resistance to targeted therapy in lung cancer.We study oncogenic gene fusions in lung cancer including ALK, ROS1, RET and NTRK1 using molecular, cellular, genetic, and translational approaches to elucidate both the sensitivity and cellular resistance to oncogene-targeted therapy. We utilize cell line and animal models of lung cancer and have derived several new human cell lines from lung tumors harboring oncogenic fusions. This research is facilitated by two IRB-approved protocols that support our translational research in oncogene-directed therapies in lung cancer:(1) that directs analysis of pre- and post-targeted therapy tumor samples to study mechanisms of tumor cell resistance to targeted therapies and (2) that allows collection of clinical data on lung cancer patients who have undergone molecular testing. Ultimately, our goal is to advance personalized medicine through the identification and analysis of driver oncogenes in lung cancer in order to improve the clinical outcomes of patients with this disease.
Vaishnavi A, Capelletti M, Le AT, Kako S, Butaney M, Ercan D, Mahale S, Davies KD, Aisner DL, Pilling AB, Berge EM, Kim J, Sasaki H, Park S, Kryukov G, Garraway LA, Hammerman PS, Haas J, Andrew SW, Lipson D, Stephens PJ, Miller VA, Varella-Garcia M, Jänne PA, Doebele RC. Oncogenic and drug sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013 Nov;19(11):1469-72.
Davies KD, Mahale S, Astling DP, Aisner DL, Le AT, Hinz TK, Vaishnavi A, Bunn PA, Heasley L, Tan AC, Camidge DR, Varella-Garcia M, Doebele RC. Resistance to ROS1 Inhibition Mediated by EGFR Pathway Activation in Non-Small Cell Lung Cancer. PLoS One, in press.
Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM, Terracciano LM, Cappuzzo F, Incarbone M, Roncalli M, Alloisio M, Santoro A, Camidge DR, Varella-Garcia M, and Doebele RC. Identifying and Targeting ROS1 Gene Fusions in Non-Small Cell Lung Cancer. Clin Can Res, 2012 Sep 1;18(17):4570-9. PMID: 22919003
Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, Kondo KL, Linderman D, Heasley LE, Franklin WA, Varella-Garcia M, and Camidge DR. Mechanisms of Resistance to Crizotinib in Patients with ALK Gene Rearranged Non-Small Cell Lung Cancer. Clin Cancer Res. 2012 Mar 1;18(5):1472-82. PMID: 22235099, PMCID: PMC3311875.
V Foundation for Cancer Research, V Scholar Award
Hope Foundation, SWOG Development Award
Paul Calabresi Clinical Oncology Scholar Award (K12)
Colorado Bioscience Discovery Evaluation Grant (BDEG)
Colorado Clinical & Translational Sciences Institute