Date on Master's Thesis/Doctoral Dissertation
8-2023
Document Type
Master's Thesis
Degree Name
M.S.
Department
Pharmacology and Toxicology
Degree Program
Pharmacology and Toxicology, MS
Committee Chair
Clark, Geoffrey J.
Committee Member
Donninger, Howard
Committee Member
Beverly, Levi
Committee Member
Ceresa, Brian P.
Committee Member
Mitchell, Robert A.
Author's Keywords
RAS; Luminal B; breast cancer
Abstract
Historically, the RAS oncoprotein has not been implicated in breast cancer due to less than 1% of breast cancer cases bearing oncogenic RAS mutations. Recently, however, it has been reported that greater than 60% of Luminal B breast cancer cases have a decreased expression of negative RAS regulators RASAL2 and DAB2IP. Thus, in many Luminal B breast cancers, RAS remains in a constitutively active state without mutation, in turn driving oncogenesis. To date, there are no FDA-approved direct inhibitors of wild type RAS. We have developed a direct RAS inhibitor that acts on wild type RAS using in silico drug library screening. Using in vitro and in vivo model systems as proof-of-principle experiments, we have demonstrated our compound to inhibit anchorage-independent growth and RAS-mediated signaling in vitro, as well as decrease Luminal B cell tumor growth rate in vivo.
Recommended Citation
Jigo, Raphael Ngozichi, "Inhibition of RAS as a novel therapeutic approach in Luminal B breast cancer." (2023). Electronic Theses and Dissertations. Paper 4150.
https://doi.org/10.18297/etd/4150
