Carlos Perez-Stable, Ph.D.
Research Associate Professor of Medicine
Description of Research
Dr. Perez-Stable discovered long-term interest in experimental therapeutics of prostate cancer (PCa) is summarized as follows: 1) development and utilization of the FG/Tag transgenic mouse model to understand the molecular events in the initiation and progression of aggressive PCa and for testing chemotherapeutic drugs singly and in combination; 2) identification of cyclin B1 (mitotic cell cycle protein) as a potential biomarker and target for PCa response to chemotherapy; 3) microtubule inhibitor drugs 2-methoxyestradiol, paclitaxel, and docetaxel require activation of cyclin B1/Cdk1 and mitotic cell cycle block to induce apoptosis in PCa cells; 4) low dose 2-methoxyestradiol + docetaxel combinations may provide a treatment strategy that can improve therapeutic efficacy against castration-resistant PCa (CRPC) while reducing toxicity often seen in patients treated with docetaxel; 5) combination of antimitotic agents with betulinic acid (BA, plant derived anti-cancer agent), an activator of NF-κB, may promote the pro-death responses in a greater variety of PCa cells, notably in the aggressive CRPC that does not respond to conventional therapies; 6) combination of docetaxel with ABT-737, a small molecule that disrupts the anti-apoptotic function of Bcl-2/Bcl-xL, can overcome the block in apoptosis present in CRPC cells; 7) combination of more potent 2-methoxyestradiol analog ENMD-1198 and BA provides an effective treatment for advanced metastatic CRPC in vitro and in TRAMP transgenic mice; and 8) BA-mediated inhibition of multiple deubiquitinases (DUBs) and induction of apoptotic cell death specifically in PCa but not in non-cancer cells and tissues may provide an effective non-toxic and clinically selective agent for chemotherapy.
- Developed a transgenic mouse model of metastatic prostate cancer used to test chemotherapeutic agents and their combinations.
- Determined that higher levels of the mitotic protein cyclin B1 in PCa cells may be a good prognostic marker for chemotherapy
- Identified a combination treatment strategy of antimitotic agents with an activator of NF-B (BA) that can increase cell death in all types of PCa cells in vitro.
- Discovered that BA inhibits multiple DUBs, inhibits TRAMP PCa tumor growth, increases apoptosis, and decreases proliferation and angiogenesis but without toxic side effects to normal tissues.