Abstract 673: Mechanisms of drugs in ovarian cancer and prevention of invasion and metastasis

Abstract

Abstract Introduction: Ovarian cancer patients are typically diagnosed late stage after the cancer has left the primary site, this is the major factor contributing to the 70% 5-year mortality rate. Standard of care is Platinum therapies or debulking surgery followed by maintenance therapies to keep cancer from coming back. The limitation to these therapies is overall toxicity to the patient forcing them to stop treatments or eventual resistance to the therapy. The objective of this study is to evaluate the mechanisms in which the novel drug, SHetA2, alone compares to the competitor, Olaparib. Additionally, discover the genetic differences between attached tumor and floating tumor in ascites.Objective: Our objective was to evaluate the mechanisms in which the novel drug, SHetA2, alone compares to the front-line competitor, Olaparib, in affecting Filamin A and cyclin d1 levels in ovarian cancer. Methods: Individual and combination drug treatments were preformed on two ovarian cancer cell lines and patient samples for cell viability assays. Immunocytochemistry was performed to visualize colocalization of proteins. RNA isolation was performed for Nanostring analysis. Results: Ovarian cancer cells treated with SHetA2 or olaparib demonstrate a decrease of cyclin D1 on the membrane colocalized with filamin A, a structural protein that facilitates movement by acting as a signaling molecule for downstream effects. Nanostring analysis of attached tumor and spheroids form ascites shows significant differential gene expression in tumor versus ascites. Conclusions: These results suggest the decrease of cyclin D1 with filamin A upon treatment with SHetA2 or olaparib could be one of the primary factors leading to each drug’s efficacy and additivity with each other. The differential gene expression of tumor versus ascites begins to elucidate the fundamental differences between attached and floating tumors and spheroids. Citation Format: Laura F. Mortan, Doris Benbrook. Mechanisms of drugs in ovarian cancer and prevention of invasion and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 673.