Characterization of intratumoral genetic heterogeneity as a predictive biomarker of response to neoadjuvant chemoradiotherapy in patients with Rectal Cancer

• Grant number: 22/03631-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2022
• End date: April 30, 2025
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Rodrigo Oliva Perez
• Grantee: Vandeclecio Lira da Silva
• Host Institution: Hospital de Beneficência Portuguesa de São Paulo. Real e Benemérita Associação Portuguesa de Beneficência de São Paulo (RBAPB). São Paulo , SP, Brazil
• Associated research grant: 18/15582-9 - Complete tumor regression in rectal cancer patients after neoadjuvant chemoradiation: molecular prediction of tumor response based on intratumoral heterogeneity and assessment of response by circulating tumoral DNA, AP.JP2

Abstract

One third of patients diagnosed with Colorectal Cancer have a rectal cancer. After treatment, some patients experience complete tumor eradication (complete response), while others experience varying degrees of tumor regression (incomplete response), and others simply do not respond. Clinical and radiological assessment of the response does not allow accurate identification of patients with a complete response. For this reason, the discovery of molecular biomarkers predictive of response can impact clinical practice in order to allow a correct and more accurate stratification of patients capable of benefiting from neoadjuvant treatment. Rectal Cancer has significant Intratumoral Genetic Heterogeneity (ITGH). Therefore, we intend to characterize, using next generation sequencing and bioinformatics tools, the genetic heterogeneity in Rectal Cancer from patients with complete response vs. incomplete. Thus, we intend to identify treatment-resistant tumor subpopulations by comparing the genetic alterations, both from a qualitative and quantitative point of view, present in tumor samples from the same patient before and after neoadjuvant treatment. The identification of genetic alterations associated with resistance to neoadjuvant treatment will provide important information about the molecular mechanisms of resistance, which may eventually lead to the identification of new therapeutic targets, increasing the possibilities and effectiveness of the treatment of Rectal Cancer. In addition, it can assist in the development of diagnostic methods allowing individualization of treatment. (AU)