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Characterization of new predictive biomarkers of response to endocrine therapy and HER2 inhibitors in breast cancer

Grant number: 19/05252-4
Support type:Regular Research Grants
Duration: October 01, 2019 - September 30, 2021
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Maria Aparecida Nagai
Grantee:Maria Aparecida Nagai
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Flavia Regina Rotea Mangone ; Maria Cristina Rodrigues Rangel ; Tharcisio Citrangulo Tortelli Junior

Abstract

Breast cancer is a complex and heterogeneous disease showing substantial variations in genetics, histopathology and clinical course of the disease and can be defined as a set of conditions with at least four distinct intrinsic molecular subtypes. Intratumoral heterogeneity is the main obstacle to treatment success and personalized medicine application. Despite rapid advancement in the molecular classification and the search for novel therapeutic targets, breast cancer treatment strategies are currently based mainly on the tumor cell positivity status for steroid hormone receptors (estrogen and progesterone) and the HER2 oncoprotein. However, regardless of the endocrine treatment offered, primary or acquired resistance affects most metastatic tumors and a significant portion of all luminal tumors. The same is true for patients with HER2+ subtype tumors, for whom complete response rates vary widely, and a considerable number of patients show resistance to target-therapy. The functional and clinical characterization of new biomarkers and the definition of the mutational processes that act during the different phases of the development and progression of the disease that allow the identification of prognostic and predictive factors of clinically relevant therapeutic response are among the areas that still need to be investigated in breast cancer. This project aims to continue the studies of identification and characterization of biomarkers performed by our group in the field of breast cancer. To this end, two subprojects will be developed with the application of different molecular and cellular techniques to evaluate the effects of the expression of PHLDA family members and RET and BCAR3 genes on the modulation of diverse biological processes and transcriptome of breast cancer cells. The main objectives are to investigate the functional role and mechanisms of action of potential new biomarkers in mammary epithelial and breast cancer cells and their potential role as a predictive factor in response to endocrine therapy and HER2 target-therapy in breast cancer. The results of this study should generate new knowledge that will improve our understanding about the role of potential new biomarkers in the process of breast tumorigenesis and its use as potential predictive biomarkers for breast cancer patients. (AU)