Deric L. Wheeler, PhD

Portrait of Deric L. Wheeler, PhD
Assistant Professor
Human Oncology
Address: 
3159 WIMR
1111 Highland Ave
Madison, WI 53705
Telephone: 
(608) 262-7837
Focus Groups: 
Cancer Biology
Education: 
PhD, Cancer Biology, University of Wisconsin, Madison, WI
Research Summary: 
Mechanisms of resistance to targeted therapies
Research Detail: 

The focus of my laboratory centers on the epidermal growth factor receptor (EGFR) which is ubiquitously expressed receptor tyrosine kinase (RTK). Upon ligand binding, the EGFR initiates a spectrum of signaling pathways that promote cell proliferation, differentiation, migration, motility, and cellular adhesion. The EGFR is recognized as a key mediator of proliferation and progression in many human tumors and strategies to inhibit EGFR signaling have emerged as highly promising cancer therapy approaches. Following more than 20 years of preclinical development, five EGFR inhibitors, two monoclonal antibodies and three small molecule tyrosine kinase inhibitors (TKIs), have recently gained FDA approval in oncology (cetuximab, panitumumab, erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated major tumor regressions in approximately 10-20% of advanced cancer patients. However, many tumors do not show response to EGFR inhibition and some of the responders eventually manifest resistance to treatment. The underlying mechanisms of intrinsic and acquired resistance to EGFR inhibitors remain largely unexplored.

In an effort to examine mechanisms of acquired resistance to EGFR inhibition we have developed a series of cetuximab-resistant cancer cell lines (H&NSCC1 and NCI-H226) models to elucidate molecular pathways leading to resistance to targeted therapies. We have found that tumors that develop resistance to cetuximab have increased nuclear EGFR where it performs discrete functions enhancing resistance to cetuximab therapy. The overall goal is to elucidate pathways that resistant tumors have activated and aim at blocking these pathways and restoring sensitivity to the original target agents.

Selected Publications: 
Toni M Brand, Mari Iida, Neha Luthar, Megan M Starr, Evan J Huppert, Deric L Wheeler. Nuclear EGFR as a molecular target in cancer. Radiother Oncol: 2013; [PubMed:23830194]
Deric L Wheeler, Ajit K Verma, Mitchell F Denning. Mouse models of the skin: models to define mechanisms of skin carcinogenesis. J Skin Cancer: 2013, 2013();971495. [PubMed:23819053]
Mari Iida, Toni M Brand, David A Campbell, Megan M Starr, Neha Luthar, Anne M Traynor, Deric L Wheeler. Targeting AKT with the allosteric AKT inhibitor MK-2206 in non-small cell lung cancer cells with acquired resistance to cetuximab. Cancer Biol. Ther.: 2013, 14(6);481-91. [PubMed:23760490]
Anne M Traynor, Tracey L Weigel, Kurt R Oettel, David T Yang, Chong Zhang, Kyungmann Kim, Ravi Salgia, Mari Iida, Toni M Brand, Tien Hoang, Toby C Campbell, Hilary R Hernan, Deric L Wheeler. Nuclear EGFR protein expression predicts poor survival in early stage non-small cell lung cancer. Lung Cancer: 2013; [PubMed:23628526]
Paul A Clark, Mari Iida, Daniel M Treisman, Haviryaji Kalluri, Sathyapriya Ezhilan, Michael Zorniak, Deric L Wheeler, John S Kuo. Activation of Multiple ERBB Family Receptors Mediates Glioblastoma Cancer Stem-like Cell Resistance to EGFR-Targeted Inhibition. Neoplasia: 2012, 14(5);420-8. [PubMed:22745588]
Toni M Brand, Deric L Wheeler. KRAS mutant colorectal tumors: Past and present. Small Gtpases: 2012, 3(1);34-9. [PubMed:22714415]
M Iida, T M Brand, D A Campbell, C Li, D L Wheeler. Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor. Oncogene: 2012; [PubMed:22430206]
Tim J Kruser, Anne M Traynor, Deric L Wheeler The use of single-agent dasatinib in molecularly unselected non-small-cell lung cancer patients. Expert Opin Investig Drugs: 2011, 20(2);305-7 [PubMed:21204748]
Toni M Brand, Deric L Wheeler Treating PIK3CA and EGFR overexpressing breast cancers with lithium citrate. Cancer Biol. Ther.: 2011, 11(3);368-70 [PubMed:21228636]
Toni M Brand, Mari Iida, Deric L Wheeler Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol. Ther.: 2011, 11(9);777-92 [PubMed:21293176]