Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
Steroid receptors play key roles in multiple pathologies, and as such, are common targets for therapeutic intervention. This is exemplified in breast and prostate cancer treatments, where drugs that target estrogen receptor (ER) and androgen receptor (AR) signaling pathways have significantly improved patient outcomes. Though the acquisition of therapy resistance remains a common clinical challenge, the persistent expression of these receptors in recurrent tumors and the success of combined therapies that target distinct regulatory pathways lends hope to development of new complementary therapies that take advantage of insight gained from mechanistic studies of how these receptor pathways can be modulated. Ubiquitylation is an emerging arena for targeted therapies. Ubiquitin, a small protein that covalently modifies substrates, can modulate receptors at multiple mechanistic levels. Most prominent is the role of ubiquitin modification in the turnover and stability of receptor proteins. The regulation of receptors by the ubiquitin-proteasome system (UPS), has given rise to a class of degrader compounds, SERDS and SARDs, many of which are now in clinical trial. New areas that are evolving in the field exploit the broader activities of inhibitors of the ubiquitin-proteasome system that also affect receptor synthesis and transcriptional signaling. Chemical biology and small molecule inhibitors are also making strides toward targeting components of the ubiquitin machinery. Evidence highlighting mechanisms by which ubiquitin and UPS inhibitors regulate ER and AR biology in cancer will be presented.
