The Schaufele laboratory has a long-standing research interest in the mechanisms of action of hormones and their receptors. Emphasis has been on the regulation of global, tissue-specific gene expression patterns by DNA-binding transcription factors, including nuclear receptors, and their co-factors. In the nuclear receptor field, our studies on androgen and estrogen receptors have been oriented towards understanding their basic mechanisms of action and their roles as central regulators of the growth, respectively, of the majority of breast tumors and almost all prostate tumors. This led to the development of high throughput, highly quantitative capabilities for rapidly identifying agents that up- or down-regulate receptor activity.

We currently are incorporating that experience into a research program designed to identify new classes of pharmaceuticals for the treatment of advanced prostate cancer. The growth of those tumors is strongly driven by abnormal activation of the androgen receptor. Most of those tumors initially respond to currently available androgen receptor-targeted drugs. But the tumors change over time in ways in which the drugs no longer are effective and, when a patient becomes resistant to all available drugs, the tumor unfortunately becomes lethal. Most tumors that develop such drug ‘resistance’ still rely on androgen receptors for their growth. Our research program is oriented towards creating a new class of drugs that blocks a specific variant of the androgen receptor that arises during the development of treatment resistance but that lacks the binding sites for currently available drugs. The aim of these studies is to prolong the success of prostate cancer treatment, hopefully indefinitely.