Identification of proteins modulating oncogenic signaling in non-resectable liver metastases resistant to systemic therapy

• Grant number: 21/01298-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2021
• End date: May 31, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Fabio Albuquerque Marchi
• Grantee: Daniela Bizinelli
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Colon cancer is a leading cause of cancer death worldwide and approximately 50% of patients develop liver metastases during the course of the disease. Although surgical resection provides a 5-year survival rate around 40%, most patients have non-resectable disease at diagnosis. In this case, the scenario is devastating due to the resistance of tumor cells to standard treatment with chemotherapy and/or monoclonal antibody. Despite the advances achieved by genomic screening of metastases, the knowledge about the global profile of proteins that potentially modulate oncogenic signaling, and which may be involved with the intrinsic resistance of tumor cells, is still limited. Considering the enormous potential for discovery and innovation that can be achieved, this project proposes the proteomic characterization of colon cancer liver metastases resistant to systemic therapy in search of promising targets that can be explored in novel therapeutic options. The main methodological steps include (1) mass spectrometry of 30 paired biopsy samples, of which 15 are non-resectable colon cancer liver metastases with progression to the first-line therapy in less than 3 months and 15 non-neoplastic tissues, (2) multidimensional integrative analysis to investigate potential modulators of oncogenic signaling associated with resistance to therapy and (3) investigation of targets identified in 100 colon cancer metastases, responder and non-responder profile, using MALDI technology. We believe that this project will allow the discovery of an unprecedented proteomic profile in colon cancer liver metastases, revealing potential modulators of tumor signaling that can be explored in different therapeutic options and provide long-term survival to patients. (AU)