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Honors thesis poster presentation.
RAS, one of the most prevalent oncogenes, is mutated in 27% of human cancers. Gainof- function RAS mutations activate multiple downstream pathways, including the RASRAF- MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. The RAS proteins KRAS, HRAS, and NRAS along with their downstream effectors are attractive targets for cancer therapy since they act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was developed in Dr. Gary Piazza's Drug Discovery Research Center at the Mitchell Cancer Institute. As a pan-RAS inhibitor, MCI-062 is hypothesized to serve as a targeted therapy for RAS-mutant cancers regardless of mutation isoform, including all types of KRAS-mutant lung cancers. The inhibitory effects of MCI-062 were tested on the growth and proliferation of two non-small cell lung cancer cell lines, A549 and H358, using colony formation assays. The cells were plated onto 12-well plates, treated with varying concentrations of MCI-062 in duplicate, and then digitally imaged and analyzed. A549 cells have a KRASG13D mutation, while H358 cells have a KRASG12C mutation. The results indicate that MCI-062 effectively suppresses the growth and proliferation of both A549 and H358 cells despite their differing mutation isoforms, suggesting that MCI-062 successfully functions as a pan-RAS inhibitor.
RAS proteins, pan-RAS inhibitor, cancer therapy, targeted therapy, lung cancer, colorectal cancer, pancreatic cancer, cell mutation
Medical Biochemistry | Medical Cell Biology | Medical Molecular Biology | Medical Sciences | Medical Specialties | Medicine and Health Sciences | Oncology
Fu, Richard, "Applying MCI-062, a Novel Pan-RAS Inhibitor, to Treat KRAS-Mutant Lung Cancer." (2022). Poster Presentations. 4.