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

• Grant number: 21/04920-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2022
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ludmilla Thomé Domingos Chinen
• Grantee: Anna Paula Carreta Ruano
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated scholarship(s): 23/01191-6 - Natural phenomena (trogocytosis and cell fusion) between ovarian cancer and immune system cells, BE.EP.DD

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TORRES, JACQUELINE APARECIDA; BRITO, ANGELO BORSARELLI CARVALHO; SILVA, VIRGILIO SOUZA E; MESSIAS, IARA MONIQUE; BRAUN, ALEXCIA CAMILA; RUANO, ANNA PAULA CARRETA; BUIM, MARCILEI E. C.; CARRARO, DIRCE MARIA; CHINEN, LUDMILLA THOME DOMINGOS. CD47 Expression in Circulating Tumor Cells and Circulating Tumor Microemboli from Non-Small Cell Lung Cancer Patients Is a Poor Prognosis Factor. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 15, p. 16-pg., 2023-08-01. (13/23277-8, 14/50943-1, 21/04920-3, 19/18100-8)

RUANO, ANNA PAULA CARRETA; COSTA, DANIELA DE JESUS FERREIRA; BRAUN, ALEXCIA CAMILA; TORRES, JACQUELINE APARECIDA; BARBOSA, PEDRO HENRIQUE PEREIRA; ABDALLAH, EMNE ALI; BARBERAN, CAROLINE; SILVA, VIRGILIO SOUZA E.; BOVOLIM, GRAZIELE; BUIM, MARCILEI E. C.; et al. HPV virus and biomarkers of resistance to chemoradiation in circulating tumor cells from patients with squamous cell carcinoma of the anus. PATHOLOGY RESEARCH AND PRACTICE, v. 243, p. 8-pg., 2023-01-31. (15/16952-6, 21/01938-9, 21/04920-3, 19/18100-8, 19/04150-3)