Poster Title

Pt-Mal-LHRH, a Newly Synthesized Compound Attenuating Breast Cancer Tumor Growth and Metastasis by Targeting Overexpression of the LHRH Receptor.

Grade Level at Time of Presentation

Senior

Major

Biomedical Sciences

Minor

Chemistry

2nd Grade Level at Time of Presentation

Junior

2nd Student Major

Biomedical Sciences

2nd Student Minor

Chemistry

Institution

Eastern Kentucky University

KY House District #

56;57

KY Senate District #

7

Department

Biology

Abstract

In the United States one in eight women will be afflicted with breast cancer. Triple negative breast cancers (TNBC) account for 10-20% of all breast cancers and are significantly more aggressive than other subtypes. There are minimal treatment therapies for TNBC due to a lack of expression of the ER, PR, and HER-2/neu receptors. Our recent work revolves around developing a novel chemotherapeutic agent that will specifically target TNBCs while exhibiting reduced systemic distribution to healthy cell.

Studies have shown the luteinizing hormone-releasing hormone (LHRH) receptor is overexpressed on 4T1 and MDA-MB-231 cells. We have designed and synthesized a Pt-Mal-LHRH compound that attaches the LHRH peptide to cisplatin to selectively target and deliver platinum to the cancer cells. Platinum is used in chemotherapy in common compounds such as cisplatin and carboplatin, however, both of these compounds elicit debilitating side effects without targeting TNBCs. Moreover, cisplatin has high rates of resistance in patients.

To address, whether Pt-Mal-LHRH is more selective and therapeutic than carboplatin and cisplatin we tested our compoundin-vivo. First, we verified the therapeutic index of Pt-Mal-LHRH and found it to be safer than cisplatin. There was no toxicity induced from 2.5-40 mg/kg injection doses, however, lethality for cisplatin is around 11 mg/kg. Further, we found that Pt-Mal-LHRH does exhibit immune suppression, which is similar to other chemotherapies, however, it does not reduce it below basal. Lastly, we compared Pt-Mal-LHRH to carboplatin and found that it is significantly more effective at reducing tumor size at doses 2.5-20mg/kg. Taken together we have found that Pt-Mal-LHRH is therapeutically more effective at reducing tumor size compared to carboplatin, while, showing a safer toxicity profile than cisplatin.

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Pt-Mal-LHRH, a Newly Synthesized Compound Attenuating Breast Cancer Tumor Growth and Metastasis by Targeting Overexpression of the LHRH Receptor.

In the United States one in eight women will be afflicted with breast cancer. Triple negative breast cancers (TNBC) account for 10-20% of all breast cancers and are significantly more aggressive than other subtypes. There are minimal treatment therapies for TNBC due to a lack of expression of the ER, PR, and HER-2/neu receptors. Our recent work revolves around developing a novel chemotherapeutic agent that will specifically target TNBCs while exhibiting reduced systemic distribution to healthy cell.

Studies have shown the luteinizing hormone-releasing hormone (LHRH) receptor is overexpressed on 4T1 and MDA-MB-231 cells. We have designed and synthesized a Pt-Mal-LHRH compound that attaches the LHRH peptide to cisplatin to selectively target and deliver platinum to the cancer cells. Platinum is used in chemotherapy in common compounds such as cisplatin and carboplatin, however, both of these compounds elicit debilitating side effects without targeting TNBCs. Moreover, cisplatin has high rates of resistance in patients.

To address, whether Pt-Mal-LHRH is more selective and therapeutic than carboplatin and cisplatin we tested our compoundin-vivo. First, we verified the therapeutic index of Pt-Mal-LHRH and found it to be safer than cisplatin. There was no toxicity induced from 2.5-40 mg/kg injection doses, however, lethality for cisplatin is around 11 mg/kg. Further, we found that Pt-Mal-LHRH does exhibit immune suppression, which is similar to other chemotherapies, however, it does not reduce it below basal. Lastly, we compared Pt-Mal-LHRH to carboplatin and found that it is significantly more effective at reducing tumor size at doses 2.5-20mg/kg. Taken together we have found that Pt-Mal-LHRH is therapeutically more effective at reducing tumor size compared to carboplatin, while, showing a safer toxicity profile than cisplatin.