Cellular Targeting of Metastatic Ovarian Cancer
Grade Level at Time of Presentation
Senior
Major
Biomedical Sciences
Minor
Mathematics and Chemistry
2nd Grade Level at Time of Presentation
Junior
2nd Student Major
Biomedical Science
Institution
Eastern Kentucky University
KY House District #
81
KY Senate District #
34
Faculty Advisor/ Mentor
Dr. Lindsay Calderon
Department
Dept. Biological Sciences
Abstract
Every year in the United States, an estimated 22,000 women will receive an ovarian cancer diagnosis and of those, an estimated 14,000 will fall fatal to the disease. Ovarian cancer accounts for more deaths than any other female reproductive cancer, ranking fifth in cancer deaths among women. Due to the nature of the disease, ovarian cancer is often difficult to detect in its early stages, limiting treatment options. Our recent work is focused on the development of a novel chemotherapeutic agent that will specifically target ovarian cancer cells while also exhibiting a reduction in deleterious side effects.
Previous studies have shown an overexpression of the luteinizing hormone-releasing hormone (LHRH) receptor on A2780 and A2780-cis cells. We have designed and synthesized a selective chemotherapeutic agent, Pt-Mal-LHRH, to target this receptor. Pt-Mal-LHRH attaches the LHRH peptide to cisplatin to selectively target and deliver cisplatin to the cancer cells. Platinum is used in common chemotherapeutic agents such as cisplatin and carboplatin, however, both compounds elicit detrimental side effects without targeting ovarian cancers. Further, cisplatin has high rate of resistance formation in patients.
To address whether Pt-Mal-LHRH is more selective agent than carboplatin and cisplatin, a drug uptake assay was conducted. The assay screened for platinum concentrations within the cells to show disruption and cessation of cancer growth. This assay was completed using both the A2780 and A2780-cis line of cells. The results of the assay suggest that there is a significant increase in uptake of Pt-Mal-LHRH in comparison to carboplatin in both the A2780 and A2780-cis cells. The assay further suggests that in the A2780-cis line there is a significant increase in uptake of Pt-Mal-LHRH in comparison to cisplatin.
Cellular Targeting of Metastatic Ovarian Cancer
Every year in the United States, an estimated 22,000 women will receive an ovarian cancer diagnosis and of those, an estimated 14,000 will fall fatal to the disease. Ovarian cancer accounts for more deaths than any other female reproductive cancer, ranking fifth in cancer deaths among women. Due to the nature of the disease, ovarian cancer is often difficult to detect in its early stages, limiting treatment options. Our recent work is focused on the development of a novel chemotherapeutic agent that will specifically target ovarian cancer cells while also exhibiting a reduction in deleterious side effects.
Previous studies have shown an overexpression of the luteinizing hormone-releasing hormone (LHRH) receptor on A2780 and A2780-cis cells. We have designed and synthesized a selective chemotherapeutic agent, Pt-Mal-LHRH, to target this receptor. Pt-Mal-LHRH attaches the LHRH peptide to cisplatin to selectively target and deliver cisplatin to the cancer cells. Platinum is used in common chemotherapeutic agents such as cisplatin and carboplatin, however, both compounds elicit detrimental side effects without targeting ovarian cancers. Further, cisplatin has high rate of resistance formation in patients.
To address whether Pt-Mal-LHRH is more selective agent than carboplatin and cisplatin, a drug uptake assay was conducted. The assay screened for platinum concentrations within the cells to show disruption and cessation of cancer growth. This assay was completed using both the A2780 and A2780-cis line of cells. The results of the assay suggest that there is a significant increase in uptake of Pt-Mal-LHRH in comparison to carboplatin in both the A2780 and A2780-cis cells. The assay further suggests that in the A2780-cis line there is a significant increase in uptake of Pt-Mal-LHRH in comparison to cisplatin.