Buenos Aires
Breast Cancer
Symposium

BA-BCS 2024

September 3 – 6, 2024

IFIBYNE Auditorium, FCEN-UBA

Poster No. 68

Use of ascitic fluid from patients to evaluate the mechanisms of action of PARP inhibitors

Moyano, Ginette1; Mares Ahlers, Candelaria1; Menay, Florencia2; Ernst, Glenda3; Real, Jorgelina Nelly3; Korbenfeld, Ernesto3; Iglesias, Brenda4; Madauss, Kevin5; Sterle, Helena2; Cayrol, Florencia2; Cremaschi, Graciela2; Mansilla, Sabrina Florencia1; Gottifredi, Vanesa1.

1- Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires, CONICET 2- Instituto de Investigaciones Biomédicas, UCA, CONICET. 3-Hospital Británico, Buenos Aires, Argentina. 4-GlaxoSmithKline, Oncology R&D, London, United Kingdom. 5- GlaxoSmithKline, Global Health R&D, Upper Providence, PA, United States

Presenting Autor:
Moyano, Ginette

Fundacion Instituto Leloir

High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of epithelial ovarian cancers (EOC), accounting for 70% of them (1). Approximately 50% of HGSOCs are associated with abnormalities in the homologous recombination (HR) pathway, such as mutations in breast cancer genes 1 and 2 (BRCA1 and BRCA2), resulting in defective repair of the DNA which is known as “homologous recombination deficiency” (2). Furthermore, advanced stages of ovarian cancer are frequently associated with the accumulation of ascitic fluid in the patient’s abdomen, known as ascites, which is made up of cellular and acellular components (3). This provides a direct source of patient tumor cells. Once surgically removed, ascitic fluid has no value from a clinical perspective, but provides a source of tumor cells directly from patients, which can be used to validate results obtained from commercial cell line assays. Likewise, they are useful to evaluate their sensitivity to different drugs, in our case, the poly ADP-ribose polymerase (PARPi) inhibitors Olaparib and Niraparib, which are a therapeutic strategy used to generate selective lethality of HR-deficient tumor cells. We have established a work protocol with the objective of generating primary cultures from tumor patient cells derived from ascitic fluid. Compared to other cancer types, primary cultures of ovarian cancer cells are relatively easy to obtain and establish in vitro due to their high viability, strong surface adhesion, and rapid cell division (4). Using serial trypsinizations we were able to select the tumor cells and eliminate the rest of the cell populations. We performed in vitro assays on already established primary cultures, which allowed us to characterize key markers for this type of tumor, such as HR, BRCA, p53, and CK7 status. We are currently evaluating the effect of different PARPi, looking for possible correlations between sensitivity to these drugs and the aforementioned markers.

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