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Robert C. Doebele, M.D., Ph.D.

Associate Professor, Division of Medical Oncology


Robert C. Doebele , MD, PhD

  

Education
Princeton University (Princeton, NJ) A.B. Molecular Biology - 1993
University of Pennsylvania (Philadelphia, PA) MD, PhD in Immunology– 2001
University of Chicago (Chicago, IL) Internal Medicine Residency and Medical Oncology Fellowship

Bio 
Dr. Doebele joined the faculty at University of Colorado Denver in July of 2008 as a member of the Thoracic Malignancies Program.  He is currently Associate Professor of Medicine. He is co-founded and co-directs the University of Colorado Molecular Tumor Board, is Scientific Lead for ORIEN at the University of Colorado, and a co-PI of the University of Colorado Lung Cancer SPORE.  He is also a Senior Editor at the AACR journal Clinical Cancer Research. Dr. Doebele is a recipient of the 2011 Boettcher Webb-Waring Biomedical Award and the 2013 V Foundation for Cancer Research, V Scholar Award.​

Research
Dr. Doebele is a physician-scientist who leads a translational research laboratory. The overall focus of my laboratory is the study of oncogenes in lung cancer. We use genetic, proteomic, and pharmacologic approaches to elucidate both the sensitivity and cellular resistance to oncogene-targeted therapy. I am the PI on 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 that has allowed us to delineate mechanisms of tumor cell resistance to targeted therapies and derive numerous new oncogene-drive human-derived cancer cell lines and (2) that allows collection of clinical data on lung cancer patients who have undergone molecular testing. A major focus of my laboratory is to elucidate the adaptive mechanisms utilized by cancer cells that allow survival following targeted therapies. Ultimately, our goal is to advance personalized medicine through the identification and analysis of driver oncogenes and their signaling pathways in lung cancer in order to improve the clinical outcomes of patients with this disease. In addition to laboratory-based research, I am PI on a number of clinical trials that focus on oncogene-targeted therapy for lung and other cancers. I am committed to training future cancer researchers through my role as a training faculty member for the Cancer Biology, Pharmacology and the Medical Scientist Training Programs (MSTP). I have mentored several including tMD (residents and fellows), PhD postdoctoral fellows and graduate students throughout my career. 
 

Selected Publications​

1. Nelson-Taylor SK, Le AT, Yoo M, Schubert L, Mishall KM, Doak A, Varella-Garcia M, Tan AC, and Doebele RC. Resistance to RET-inhibition in RET-rearranged NSCLC is mediated by reactivation of RAS/MAPK signaling. Mol Cancer Ther. 2017 May 12. PMID: 28500237.

2. Vaishnavi A, Schubert L, Rix U, Marek LA, Le AT, Keysar S, Glogowska MJ, Smith MA, Kako SL, Sumi NJ, Davies KD, Ware KE, Varella-Garcia M, Haura EB, Jimeno A, Heasley LE, Aisner DL, Doebele RC. EGFR mediates responses to small molecule drugs targeting oncogenic fusion kinases. Cancer Res. 2017 Apr 20. pii: canres.0109.2017. doi: 10.1158/0008-5472.CAN-17-0109. [Epub ahead of print] PMID: 28428274

3. Couts KL, McCoach CE, Murphy D, Christiansen J, Turner J, Lewis KD, Robinson WA, Doebele RC. Acral Lentiginous Melanoma Harboring a ROS1 Gene Fusion with Clinical Response to Entrectinib. JCO Precision Oncology 2017; 1:1-7. 

4. Dziadziuszko R, Le AT, Wrona A, Jassem J, Camidge DR, Varella-Garcia M, Aisner DL, Doebele RC. An activating KIT mutation induces crizotinib resistance in ROS1 positive lung cancer. J Thorac Oncol. 2016 Aug;11(8):1273-81. PMID: 27068398.

5. Bivona TG and Doebele RC. Targeting residual disease in oncogene-driven solid cancers to convert temporary tumor control into cure. Nat Med. 2016 May 5;22(5):472-8. PMID: 27149220.

6. Doebele RC, Davis LE, Vaishnavi A, Le AT, Estrada-Bernal A, Keysar S, Jimeno A, Varella-Garcia M, Aisner DL, Li Y, Stephens PJ, Morosini D, Tuch BB, Fernandes M, Nanda N, Low JA. An oncogenic NTRK fusion in a soft tissue sarcoma patient with response to the tropomyosin-related kinase (TRK) inhibitor LOXO-101. Cancer Discov. 2015 Oct;5(10):1049-57. PMCID: PMC4635026.

7. 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. PMCID: PMC3823836

8. 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. 2013 Dec 13;8(12):e82236. PMCID: PMC3862576.

9. 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. PMCID: PMC3311875​.

PubMed Articles​ 

Funding 
Current
NIH/NCI R01 CA193935
·   The role of EGFR as a mechanism of therapeutic resistance in gene fusion positive lung cancer.
Department of Defense, Lung Cancer Research Program, Concept Award  
·   Induced tumor cell heterogeneity by the sleeping beauty transposon system to generate an improved model of drug resistance.
NIH/NCI P50 CA058187
·   SPORE in Lung Cancer
Funding from the Christine J. Burge Endowment for Lung Cancer Research at the University of Colorado Cancer Center
Funding from the Robert and Kevin Hanlon Foundation.
Past
The V Foundation for Cancer Research
·  NTRK1 gene fusions as a novel oncogene class and therapeutic target in lung cancer
Boettcher Foundation Webb-Waring Biomedical Research Award                            
·  Targeting resistance in oncogene-driven non-small cell lung cancer (NSCLC)