Loading in 2 Seconds...
Loading in 2 Seconds...
GDC-0449: From Corn Lilies to a Cure BCCNS Symposium September 19.2009. Simon S. Yoo, MD Assistant Professor of Dermatology, Otolaryngology, and Surgery Feinberg School of Medicine Northwestern University. Corn Lilies & Cyclops. 1950s – Idaho sheep ranchers noticed strange birth defects
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
Simon S. Yoo, MD
Assistant Professor of Dermatology, Otolaryngology, and Surgery
Feinberg School of Medicine
Sonic hedgehog tells the body how to develop a normal face during development of embryos
There are 3 players at play in the sonic hedgehog signaling pathway:
PTCH (or patch), SMO (smoothened), and SHH (sonic hedgehog).
After development SHH is usually quiet except during hair follicle growth in the skin.
If SHH is around, it can attach to PTCH and activate SMO to cause a number of events in the cell that can lead to cancer.
SHH can act via PTCH and other mechanisms to keep cells moving through their cycle leading to uncontrolled cell growth – a hallmark of cancer.
SMO when activated works with another protein called GLI1 (Glioma-associated oncogene homolog 1 ) to cause increased cell proliferation and decrease apoptosis or cell death.
Cyclopamine as well as GDC-0449 to inhibits SMO and therefore decrease cell proliferation and increase cell death.
Inhibition of the Hedgehog Pathway in Advanced Basal-Cell CarcinomaDaniel D. Von Hoff, M.D., Patricia M. LoRusso, D.O., Charles M. Rudin, M.D., Ph.D., Josina C. Reddy, M.D., Ph.D., Robert L. Yauch, Ph.D., Raoul Tibes, M.D., Glen J. Weiss, M.D., Mitesh J. Borad, M.D., Christine L. Hann, M.D., Ph.D., Julie R. Brahmer, M.D., Howard M. Mackey, Ph.D., Bertram L. Lum, Pharm.D., Walter C. Darbonne, M.S., James C. Marsters, Jr., Ph.D., Frederic J. de Sauvage, Ph.D., and Jennifer A. Low, M.D., Ph.D.
Phase I Multicenter Trial of GDC-0449, evaluating efficacy and safety for advanced BCC
Phase II – 20-300 subjects to assess how well the drug works as well as to continue Phase I safety assessments (if new drugs fail they fail here)
Phase II Multicenter Trial of GDC-0449, evaluating efficacy and safety for advanced BCC