Induction of chemoresistance in human breast cancer linage cells and subsequent treatment with specific target chemotherapeutic agents

• Grant number: 19/10229-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2019
• End date: July 31, 2020
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Debora Aparecida Pires de Campos Zuccari
• Grantee: Júlia Ferreira Balan
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Breast cancer is the most frequent malignant neoplasm among women. For a good prognosis, a significant challenge is tumor recurrence, which, in many cases, results from the development of resistant cells to previous chemotherapy treatment. Mechanisms such as DNA repair and the mesenchymal epithelial transition are involved with the induction of chemoresistance. The first process is responsible for maintaining the genomic integrity of the cells, enabling cell proliferation. Meanwhile, the second may be related to the generation of less differentiated cells and the emergence of cells with stem cell properties, capable of forming different clones, resulting in intratumoral heterogeneity, which, in turn, culminates in chemoresistance. In view of this scenario, stands out the importance of personalized medicine, with the use of targeted drugs, for the treatment of cancer. Thus, the aim of this study is to induce resistance in cells from breast cancer lines, MCF7 and MDA-MB-468, by treatment with carboplatin, and subsequently treat the chemoresistant cells with the target-specific drugs erlotinib and cetuximab, epidermal growth factor receptor inhibitors, and olaparib, PARP inhibitory drug. Cell viability will be assessed by means of the MTT assay (3- {4,5-dimethyl-2-thiazol-2-yl} -2,5-diphenyltetrazolium bromide). Thus, it is intended to prove the effectiveness of individualized therapies to treat chemoresistant cells, aiming at a better prognosis and increased survival of patients.