Frequency of polymorphisms in the genes responsible for the absorption, distribution, metabolism and excretion (ADME) of drugs in patients with Hepatocellular carcinoma and hepatitis C

• Grant number: 15/16291-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: May 31, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Suzane Kioko Ono
• Grantee: Suzane Kioko Ono
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Flair José Carrilho ; Vera Kim
• Associated research grant(s): 17/50042-2 - Discussion of research projects involving chronic Hepatitis B and C antiviral treatment, AP.R SPRINT

Abstract

The cytochrome P450 (CYP) enzymes are responsible for 70% to 80% of all phase I oxidative metabolism of many drugs. In addition, the polymorphism described in absorption, distribution, metabolism and excretion (ADME) genes have been associated with antitumor drugs, being relevant to the development and clinical application of new drugs. Among them we can relate the Sorafenib and erlotinib in the treatment of hepatocellular carcinoma (HCC). HCC is the fifth most common type of cancer worldwide, and around 500,000 people are affected. The oxidative metabolism of these drugs (erlotinib and sorafenib) in the treatment of HCC is mediated by ADME enzymes. Due to better identification of these mechanisms can open new mechanisms for prevention and treatment of HCC. As the development of more efficient and lower toxicity therapies. In relation to hepatitis C virus (HCV), the main factor that causes the HCV to the top of the most studied diseases is the high chronicity. Around 70-85% of cases progress to chronic form and in approximately 20-40% of patients with chronic HCV develops cirrhosis after 10-20 years of infection and in 20% of cases can rise to the HCC. The treatment of chronic hepatitis C may lead reduction of inflammatory activity and disease progression. The greatest promise for the treatment of hepatitis C are the new medicines, Daclastavir, Simeprevir and Sofosbuvir approved by Agência Nacional de Vigilância Sanitária (ANVISA) and included in the Sistema Único de Saúde (SUS) in 2015, which are also metabolized by the CYP enzymes, among other proteins responsible for ADME. Our hypothesis is that the change in activity or expression of predictive ADME seems to be the key to drug efficacy/toxicity response. The aim of this study is to assess the frequency of polymorphisms of genes responsible for drug ADME in a patient with HCC and HCV, treated in the Department of Gastroenterology of Hospital das Clínicas da Faculdade de Medicina da USP (HC-FMUSP), evaluate the possibility to direct treatment in addition to starting a new type of clinical management. (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)

KIM, VERA; VAN DER WAL, THIJS; NISHI, MIRIAM YUMIE; MONTENEGRO, LUCIANA RIBEIRO; CARRILHO, FLAIR JOSE; HOSHIDA, YUJIN; ONO, SUZANE KIOKO. Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters. PHARMACOGENOMICS, v. 21, n. 9, p. 575-586, JUN 2020. (15/16291-0)