Evaluation and molecular characterization of circulatong tumor cells of Ovarian Cancer patients

Abstract

Ovarian Cancer is one of the Cancers with higher mortality in women, especially among the periods of menopause/postmenopause. Its characterization is important for diagnosis/specific treatments. Regardless of therapeutic advances, most patients succumb to the disease. Mutations of the BRCA1 or BRCA2 genes can lead to resistance to platinum-based chemotherapy. A new type of therapeutic approach is the treatment with PARP inhibitors (iPARP). However, the response has been variable due to primary or acquired resistance mechanisms. Primary tumors/metastatic lesions can release Circulating Tumor Cells (CTCs), which are highly heterogeneous. Authors have studied the cell fusion that occurs when two or more cells make up only after the fusion of cell membranes. Objective: To identify and characterize by cytopathological analysis CTCs from patients with metastatic ovarian tumor, mutated BRCA1/2 and to verify the presence of cell fusion between CTCs and leukocytes, and to verify in CTCs the presence of iPARP resistance-determining genes. Methodology: Prospective study conducted by collecting whole blood from patients (n = 25) at three time points: before, 30 and 180 days after starting treatment with Olaparibe (iPARP). The samples will be processed/filtered ISET the system. Subsequently, double-label immunocytochemistry will be performed for protein evaluation of: MC1-R, GnT-V, SPARC and analysis of the expression of iPARP-resistant genes: SLFN11, REV7, 53BP1 and CTC1 by digital PCR. Expected Results: To be able to demonstrate that the liquid biopsy through CTCs can open new possibilities for understanding the tumor biology, diagnosis and follow-up of these patients. (AU)