GU Cancers Symposium 2011: ASCO ASTRO SUO - Overview of translational aspects of drug development in prostate cancer - Session Highlights

ORLANDO, FL USA ( - This session opened with the question "how do we improve drug development, and what clues are there"?

We can improve genetic characterization, rationale for combinations of targeted therapies and non-oncogenic targets. There are more than 800 agents in clinical development, a 143% increase in 10 years. Strategies include inhibition of compensatory pathways. An example is to target the “self-sufficiency in growth signal pathway,” which is where most castration-resistant targets are. “Evading apoptosis” and “non-oncogenic stress” hallmark pathways provide multiple targets. Dr. DiPaola gave an example of autophagy, an evolutionary cellular process where the cell consumes cellular proteins to survive. Aggressive cancer depends on autophagy to reduce oxidative and metabolic stress. This occurs in Ras transformed cells in their model. Autophagy is activated during cancer progression, such as via estrogen receptor stress, or by activation using a targeted agent. An example of the latter issue is use of an Src kinase inhibitor which activates autophagy since Src has a normal cellular role in suppressing autophagy. This establishes rationale for use of autophagy inhibitors in combination therapy with other compounds. In Dr. DiPaola’s lab, Bcl-2 inhibition with ABT737 was augmented by combination with the autophagy inhibitor hydroxychloroquine. Autophagy inhibitors as monotherapy may not be as effective as using them in combination therapy, he said.

Presented by Robert S. DiPaola, MD at the 2011 Genitourinary Cancers Symposium, General Session III: Translational Science Session: New Targets for Prostate Cancer Therapy - February 17-19, 2011 - Orlando World Center Marriott in Orlando, Florida USA

The opinions expressed in this article are those of the Contributing Medical Editor and do not necessarily reflect the viewpoints of the GU Cancers Symposium, ASCO, ASTRO, or SUO