Molecular analysis of breath condensate to predict tumor response to epidermal growth factor tyrosine kinase inhibitors in lung cancer

• Grant number: 11/17772-0
• Support Opportunities: Scholarships abroad - Research
• Start date: July 02, 2012
• End date: July 01, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcelo Bezerra de Menezes
• Grantee: Marcelo Bezerra de Menezes
• Host Investigator: Noe Zamel
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Toronto (U of T), Canada

Abstract

Lung cancer is the leading cause of cancer-related deaths; survival rates of disease in advanced stages are low and this fact spurs the investigation of systemic therapies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have proven efficacy in a portion of cases of non-small cell lung cancer (NSCLC). To find out which patients could benefit from this treatment is subject of many studies, and some predictors of response have already been identified. Exhaled breath condensate (EBC) has been studied to evaluate many respiratory diseases, but not quite much concerning lung cancer. Objectives: To optimize a technique of DNA / RNA extraction from EBC and to explore molecular markers in breath condensate to predict response to TKI - erlotinib in patients with NSCLC. Materials and Methods: Patients enrolled will be the ones taking part in a phase II clinical trial already being developed at the University of Toronto (SELECT study) who undergo treatment with erlotinib. EBC will be obtained before and after therapeutic intervention by exhalation into a cooled plastic tube. DNA and RNA will be extracted from the EBC using affinity spin columns and genetic markers of responders and non-responders will be compared in order to identify markers of good response to treatment. We intend to study temporal and dynamic changes in gene expression patterns pre- and post-TKI treatment as well. Significance: We intend to develop a new non-invasive method of DNA and RNA extraction from the lung milieu using EBC. That method could be used to evaluate other respiratory diseases such as asthma and chronic obstructive pulmonary disease. Furthermore, the study may lead us to identify biomarkers of response to an ITK in NSCLC patients. (AU)