Ovarian cancer remains the most lethal of all of the gynecological cancers. Chemotherapy is the preferred treatment method; however, the development of chemoresistance by cancer cells has prevented appreciable improvement in the five-year survival rate. Upon continued recurrence, higher and higher chemotherapy doses are required for treatment, and the undesirable side effects become more pronounced, having a negative effect upon the quality of life of ovarian cancer patients. Recent studies by our lab have suggested that a new class of synthetic drugs, called DAPs (for short), could serve as a potential alternative to common chemotherapy regimens. The DAPs have significant potential, not only as a stand-alone, first line treatment for ovarian cancer, but also as a means of combating and eliminating chemotherapy-resistant cancer cells, as well. A sub-set of these drugs appear to specifically target ovarian cancer cells for elimination, while preventing damage to normal cells and tissues. This selectivity is based upon a specific cellular signaling molecule, STAT3, which is “hyperactivated” in ovarian cancer cells. This hyperactivation of STAT3 contributes to uncontrolled ovarian cancer cell growth, and an enhancement of survival.
For this study, I will continue to investigate the anticancer potential of a number of additional DAP compounds that should prove useful in combating ovarian cancer while providing protection to normal, non-cancerous cells. I will use a number of known ovarian cancer cell lines, both susceptible to chemotherapy treatment and those resistant to chemotherapy, to test the effectiveness of the DAPs. Non-cancerous ovarian epithelial cells will be used to determine toxicity towards normal cells. I will then move on to look into the precise mechanism that the most effective DAPs use to target and destroy cancer cells in both the laboratory and using computer simulations. I will also use these most promising new compounds to treat ovarian cancer in a mouse model of the disease.