Dr. Dan Theodorescu, Director of the NCI-designated Comprehensive Cancer Center at the University of Colorado, along with fellow collaborators at the University of Colorado,has identified an effective approach to target the two Ral (Ras-like) GTPase proteins, RalA and RalB, for the treatment of cancer. This research group is also developing a companion diagnostic/prognostic assay that can guide therapy, along with several lead compounds that may constitute a “first-in-class” GTPase targeted cancer therapeutic that does not rely on inhibition of post-translational protein modifications.
Dr. Theodorescu's group has identified several non-proprietary Ral inhibitors as lead candidates for drug derivatization, now the subject of ongoing development aimed at design and synthesis of a novel series of second generation Ral inhibitors with enhanced potency, specificity, and pharmacokinetic properties. Dr. Theodorescu also identified a “transcriptional signature” of 39 genes that respond to depletion of RalA and RalB in vivo, then evaluated the signature in microarray-profiled tumor cohorts. The Ral transcriptional signature score (RTSS) provides a new prognostic tool that can be evaluated and compared alongside current clinical practice, guiding therapy and aggressiveness of treatment.
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