Matthew Robinson, PhD
Office Phone: 215-728-3141
Antibodies represent an important class of targeted cancer therapies. While antibody-based therapies show efficacy against a variety of cancer types they, like targeted therapies in general, often suffer from the problem of drug resistance. The Robinson laboratory is taking two distinct, but complimentary, approaches to improve the efficacy of antibody-based therapies. The first is a direct approach of developing and implementing antibody-engineering techniques to rationally design and build antibodies with improved function. Second, we are interested in identifying the mechanisms of action associated with antibodies and determining the molecular basis by which cancer cells develop resistance to those agents.
The majority of our work focuses on the ErbB receptor tyrosine kinase family (EGFR, ErbB2/HER2, ErbB3/HER3, & ErbB4/HER4). Inappropriate activation of these receptors drives cancer formation and progression in a number of tissues. Overexpression of these proteins, as seen in ErbB2+ Breast and gastric cancers and EGFR+ head and neck cancer, correlates with aggressive disease and poor patient outcomes. This has led to the development of agents that are capable of blocking signaling through those receptors and improving patient outcomes. ErbB3, understudied as a drug target in comparison to EGFR and ErbB2, is increasingly recognized as a driver of resistance to ErbB-targeted therapies. Projects in the laboratory are focused on developing both ErbB3-targeted therapies and strategies to effectively exploit the therapeutic activity of those agents. We have also used high throughput screening approaches to identify novel components of signaling networks downstream of the ErbB receptor tyrosine kinases. Work is ongoing to understand how those proteins function within ErbB signaling networks and how those interactions can lead to drug resistance. The ultimate goal of this work is to identify treatment strategies that exploit those interactions to overcome resistance.