Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Clark, Geoffrey J.
Committee Co-Chair (if applicable)
Ceresa, Brian P.
Mitchell, Robert A.
RAS; Luminal B; breast cancer
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.
Jigo, Raphael Ngozichi, "Inhibition of RAS as a novel therapeutic approach in Luminal B breast cancer." (2023). Electronic Theses and Dissertations. Paper 4150.