Masuda Akther, MS
A Novel Combinatorial Treatment Strategy for mTORC1 Driven Tumors
Abstract
Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master regulator of cellular metabolism that drives uncontrolled cell growth in many human cancers. We previously developed a therapeutic strategy to potently and selectively kill tumor cells driven by high mTORC1 activity by targeting the guanylate nucleotide synthesis enzyme IMPDH. However, we also found that tumor cells respond to guanylate nucleotide depletion by activating specific DNA replication stress response (RSR) and DNA damage response (DDR) factors, which promote their survival. Thus, we hypothesize that inhibiting DDR/RSR kinases will enhance IMPDH inhibitor-induced tumor cell death, while maintaining selectivity, thereby shrinking or even eliminating tumors. Using both cell culture and in vivo studies, we will determine the therapeutic efficacy of this combination, as well as the underlying molecular mechanism of response, with the potential to establish a new treatment paradigm for mTORC1-driven cancers.
I’m so grateful and excited to be awarded this prestigious fellowship through the PhRMA Foundation. It gives me confidence in my path in translational research and motivates me to keep working toward discoveries that can make a real difference.
