Evaluation of microRNAs, oxidized biomolecules and polymorphisms in the CYP2E1, ABCB1 and ABCC2 genes as possible biomarkers of cisplatin-induced toxicities in head and neck cancer patients

• Grant number: 17/11329-4
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2018 - July 31, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Patricia Moriel
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Carmen Silvia Passos Lima ; Eder de Carvalho Pincinato ; Luis Antonio Salazar Navarrete ; Marília Berlofa Visacri ; Nicolás René Saavedra Cuevas

Abstract

The most effective treatment for advanced head and neck cancer is concomitant cisplatin and radiotherapy. However, its use is limited due to its toxicities caused by oxidative stress, mainly nephrotoxicity. There is a need to identify new biomarkers of nephrotoxicity. Among the biomarkers studied, we have the microRNAs and oxidized biomolecules. In addition to these possible biomarkers, the CYP2E1 enzyme, ABCB1 and ABCC2 transporters appear to be related to cisplatin-induced oxidative stress and nephrotoxicity. The objective of this study will be to analyze microRNAS and oxidized biomolecules as possible biomarkers of nephrotoxicity and to verify the relationship of polymorphisms in the CYP2E1, ABCB1 and ABCC2 genes with oxidative stress and cisplatin-induced toxicities in head and neck cancer patients. This is an analytical, experimental, clinical, single-arm, prospective, quantitative study with non-probability sampling of the consecutive type. Head and neck cancer patients who start treatment with cisplatin and radiotherapy will be included. Nephrotoxicity, gastrointestinal toxicity, myelotoxicity, expression of plasmatic and urinary microRNAs, urinary and plasmatic oxidative stress, and polymorphisms in the CYP2E1 genes (rs3813867, rs3813865, rs8192772), ABCB1 (rs1045642, rs1128503 and Rs2032582) and ABCC2 (rs717620, rs2273697 and rs3740066) will be evaluated. Treatment response, overall survival, and disease-free survival will also be evaluated. Chi-square, Fisher exact, Mann-Whitney and ANOVA tests for repeated measures will be used for statistical analysis, as well as the Hardy-Weinberg equilibrium, considering p <0.05. (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)

FRANCA QUINTANILHA, JULIA COELHO; FRANCINETTE SAAVEDRA, KATHLEEN; VISACRI, MARILIA BERLOFA; MORIEL, PATRICIA; SALAZAR, LUIS A.. Role of epigenetic mechanisms in cisplatin-induced toxicity. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 137, p. 131-142, MAY 2019. (17/11329-4, 17/02338-0)

QUINTANILHA, JULIA C. F.; CURSINO, MARIA A.; BORGES, JESSICA B.; TORSO, NADINE G.; BASTOS, LARISSA B.; OLIVEIRA, JULIANA M.; COBAXO, THIAGO S.; PINCINATO, EDER C.; HIRATA, MARIO H.; GERALDO, V, MURILO; et al. MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer. BMC CANCER, v. 21, n. 1, MAY 19 2021. (17/11329-4, 17/02338-0)

MORIEL, P.; CURSINO, M. A.; QUINTANILHA, J. C. F.; BASTOS, L. B.; OLIVEIRA, J. M. D.; TORSO, N. D. G.; LIMA, C. S. P.; VISACRI, M. B.. Associations of Genetic Polymorphisms of the Transporters with Cisplatin-Induced Renal Adverse Reactions in Patients with Head and Neck Cancer. DRUG SAFETY, v. 45, n. 10, p. 2-pg., 2022-10-01. (17/11329-4)