Deric Wheeler

Credentials: PhD

Position title: Assistant Professor


Phone: (608) 262-7837

3159 WIMR
1111 Highland Ave
Madison, WI 53705

Wheeler Lab

Focus Groups

Cancer Biology


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.

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