Squalamine & Cisplatin: Therapeutic Agents  Ovarian Ca

Squalamine and Cisplatin: Potential Ovarian Cancer Therapeutic Agents

Richard J. Pietras, M.D., Ph.D., University of California, Los Angeles

Funded by the DoD Ovarian Cancer Research Program

http://cdmrp.army.mil/highlights/default.htm#3

Squalamine, a naturally occurring antiangiogenic steroidal compound, is found in tissues of the dogfish shark. Squalamine works through the protein vascular endothelial growth factor (VEGF) signaling pathway to inhibit endothelial cell surface proliferation and new capillary formation (angiogenesis).

Squalamine also interacts with many chemotherapeutic agents and has been shown to enhance their effectiveness. Richard Pietras, a scientist from the University of California, Los Angeles, is studying a potential angiogenic role of Squalamine alone and in combination with other chemotherapeutic drugs such as cisplatin and carboplatin.

Through research funded by a DoD Ovarian Cancer Research Program Idea Development Award, Dr. Pietras has shown that Squalamine is antiangiogenic in ovarian cancer xenografts and is able to enhance the cytotoxic effects of cisplatin on ovarian cancer cells.

Dr. Pietras's research also provides evidence that ovarian tumor growth can be slowed due to the decreases in microvessel formation with Squalamine treatment. Additionally, apoptosis (killing) of ovarian cancer cells was increased in xenograft nude mice due to increases in the cytotoxic effects of cisplatin in combination with Squalamine.

Dr. Pietras's preclinical studies in xenograft nude mouse models and ovarian cancer cells helped promote the initiation of clinical-translational Phase II trials of Squlamine for the treatment of patients with ovarian cancer. Squalamine shows great promise for the treatment of women afflicted with ovarian cancer.

Publications:

Li D, Williams JI, and Pietras RJ. 2002. Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression. Oncogene 21:2805-2814.

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