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OVARIAN CANCER MONOTHERAPY                                                                

In Vitro Efficacy

Prolanta has the possibility of becoming a major breakthrough for ovarian cancer. Prolanta targets multiple signaling pathways and has both anti-prolactin and anti-HER2 activity, which are relevant targets for ovarian cancer. Therefore, Prolanta has the potential to become a very significant targeted therapy for ovarian cancer. Currently, cytotoxic drugs (chemotherapy) are the only drugs approved for this deadly disease.

Prolactin (PRL) is a neuroendocrine hormone involved in the development, differentiation and function of the mammary gland and ovary, and its biological activities are mediated by a specific membrane receptor, the PRL receptor (PRLR).
PRL has been shown to potently induce proliferation in several ovarian cancer cell lines and activates the ras oncogene in these cells. Research conducted by scientists at MD Anderson has demonstrated beneficial modulatory effects of Prolanta on critical intracellular signaling pathways important in the pathogenesis of cancer. In an orthotopic xenograft mouse model of ovarian cancer, the data shows a dose-dependent reduction in tumor growth.

Research performed in Dr. Anil Sood’s laboratory at MD Anderson has shown that the PRLR protein is expressed in vitro in 8 of the 9 ovarian cancer cell lines evaluated.  Treatment with Prolanta inhibited the phosphorylation (activation) of both MAPK and AKT in two different ovarian cancer cell lines in vitro.
A dose-range finding study of Prolanta was conducted in a xenograft mouse model.  One million SKOV3 human ovarian adenocarcinoma cells were injected orthotopically on Day 1.  The tumors were allowed to engraft for 7 days.  Daily intraperitoneal injections of Prolanta at 100, 200 or 400 µg per mouse per day or mannitol buffer only (control) were begun on Day 8 and continued for one month.  There were seven mice each in the control and 400 µg dose groups and eight mice each in the 100 and 200 µg dose groups. At the end of one month of dosing, the mice were sacrificed and the tumor nodules were counted and weighed.


Human ovarian cancer cell line SKOV3 implanted in nude mice

Tumor response to treatment with Prolanta (after 28 days)

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