Investigating the NAMPT-SIRT-p73 nexus as a therapeutic target for breast cancer

Rampant incidence of breast cancer has driven the search for novel scientific insights on various aspects of breast cancer. In this context and based on our recent discoveries, here we propose a clinically applicable strategy to better the diagnosis and treatment of breast cancer.It is a scientifically proven fact that the tumor suppressor proteins (for example p73) in our body can “suppress” the growth of cancer cells. To achieve this function, these tumor suppressor proteins need to be in an “active” form. Hence, the activated tumor suppressors represent a very promising anti-cancer therapeutic entity. Thus the overall objective of this project focuses on the therapeutic activation of p73 protein.Recently, we discovered that the upstream biological molecules- NAMPT and SIRTs are involved in p73 activation in breast cancer cells. We observed that whenever we activate p73 protein, breast cancer cells stop growing. Most importantly, we found that the expression of NAMPT, SIRTs and p73 genes is associated with the survival from breast cancer in 176 patients. Together, these preliminary data strongly support the diagnostic and therapeutic potential of our research. Hence, we want to comprehensively investigate NAMPT-SIRT-p73 nexus in the established models of breast cancer and patient samples. This study aligns with the Canadian Breast Cancer Foundation (CBCF)’s mission of “funding relevant and innovative research”, and upholds a vision of “creating a future without breast cancer”. To investigate the NAMPT-SIRT-p73 nexus as a therapeutic target for breast cancer1) Comprehensive dissection and characterization of the NMNATs/NAMPT-SIRTs-p73 nexus to determine its potential as a breast cancer diagnostic/prognostic marker and/or therapeutic target. 2) Therapeutic modulation of the NAD+ biosynthesis pathway through in vivo studies using various breast cancer models in mice. 3) Comprehensive analysis of the various breast cancer patient biopsy datasets and biopsy samples to understand the role of the NMNATs/NAMPT-SIRTs-p73 nexus in clinical outcome.