UWCCC 3P Laboratory needed [13C]6-bortezomib as an internal standard to develop a method to detect plasma concentrations of bortezomib for a Phase I study of Suberoyalanilide Hydroxamic Acid (SAHA) in Combination with Bortezomib in Patients with Advanced Malignancies.
SMSF synthesized and purified 13C-labeled bortezomib.
3P successfully developed the method.
David Jarrard, MD – Cell Signaling Program
NCI R01 CA97131
Induction of senescence may be useful for cancer treatment.1
HTS at SMSF identified compounds that induce senescence from a 4160 compound library (Figure).
Candidate compounds selected based on secondary assays for persistent growth arrest after drug removal and increased expression of previously described senescence marker genes.
Four compounds not previously associated with senescence identified for further investigation (diazequone, bithionol, dichlorophene, pyrithione)2
1Ewald JA, Desotelle JA, Wilding G, and Jarrard DF. Therapy-induced senescence in cancer. J Natl Cancer Inst, 2010;102(20):1536-46.
2Ewald JA, Peters N, Desotell, JA, Hoffman, FM, and Jarrard DF. A high-throughput method to identify novel senescence-inducing compounds. J Biomol Screen, 2009; 14(7):853-8.
Mark Burkard, MD, PhD – Cell Signaling Program
Mary Kay Ash Charitable Foundation Grant 013-10
Cancers harbor supernumerary chromosomes (polyploidy) that could provide a ‘targetable’ abnormality.
Derived matched diploid and tetraploid cell lines and performed a synthetic lethal siRNA screen of over 2000 targets.
A small number of siRNAs reduced 4N proliferation without affecting 2N proliferation (red box in Figure), including siRNAs to a number of potassium channels.
Potassium channel inhibitors might provide synthetic lethal effects on 4N cells and not on 2N cells and may make suitable therapeutics for polyploid cancers.