Identification of mutations in EGFR, KRAS, BRAF and NRAS genes in sputum biopsy and its correlation with tumor specimens in patients with NSCLC

• Grant number: 19/09910-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2019
• End date: May 24, 2021
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Vanessa Karen de Sá
• Grantee: Débora Souza Andrade
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated research grant: 15/26642-4 - Detection of hyaluronan and mutations in sputum liquid biopsy as screening in patient with lung cancer, AP.JP

Abstract

Lung cancer (PC) in Brazil is a pathology with a high estimate of incidence and mortality, according to data from the National Cancer Institute (INCA), with the majority of men (17,330), but a large number of women (10,890), thus totaling 28,220 people affected by it. Since they are glaring numbers, it was noted the need to develop innovative non-invasive methods for the diagnosis of patients, aiming the comfort of them. Due to the urgency of the development of these methods, research groups seek options for the diagnosis, prognosis and treatment of PC, with a focus on sputum, blood or bronchial lavage biopsies that allow a previous detection of the disease. PC is divided into two categories: small cell lung carcinoma (CPPC), where there is a lower percentage of patients (18%), and non-small cell lung cancer (NSCLC) that affects most patients (80%). From the knowledge of the mechanisms of carcinogenesis and the advances of molecular biology, specific molecular subtypes have been identified. These molecular changes are considered drivers when they are able to guide the clinical behavior of tumors. Of these mutations, we can highlight those that occur in EGFR (glycoprotein that has the role of regulation, stimulating cell proliferation and survival); KRAS (a protein that regulates normal growth signaling of cells, and also cells that become malignant); BRAF (protein responsible for differentiation, proliferation, cell growth and apoptosis of cells); NRAS (signaling protein as proliferation, cytoskeletal organization and apoptosis). With this knowledge new drugs were developed, capable of inhibiting the activation of these mutant proteins. The first successful example was seen with EGFR tyrosine kinase inhibitors in patients with the presence of specific mutations in this gene. Since then many other changes have been described and we are faced with the impressive clinical benefits of precision medicine. As a master's degree, our proposal is to detect these sputum mutation drivers of lung cancer patients through new generation sequencing and to correlate with findings in tissue biopsy and plasma, aiming the development of a new, non-invasive, detection approach of these molecular changes. (AU)