Enhancing Efficacy of Tubulin Inhibitors in Colorectal Cancers via Translesion Synthesis Inhibition
Guyette, Madison
Guyette, Madison
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Abstract
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with annual incidence increasing alarmingly in young adult populations. The development of resistance to existing chemotherapeutics plays a significant role in cancer burden. Translesion synthesis (TLS) polymerases, particularly REV1, enable cancer cells to tolerate DNA damage and contribute to therapeutic resistance and cancer formation. This study indicates that disruption of REV1 function alters ?-tubulin expression across multiple cellular models. Specifically, reduced ?-tubulin expression was observed in mouse embryonic fibroblast REV1 knockout (MEF REV1 KO) cells and in the human colorectal cancer cell lines HCT116 and HT-29 following treatment with the REV1 inhibitor, JH-RE-06. Because ?-tubulin is a critical component of microtubules required for mitotic spindle formation, its decreased expression may increase cellular vulnerability to agents that disrupt microtubule dynamics. These findings suggest that inhibition of REV1 may be a novel treatment option to sensitize CRC to tubulin inhibitors. This study therefore investigates the potential of combining TLS inhibition with tubulin inhibitors as a strategy to enhance therapeutic efficacy in CRC. Together, these findings support REV1 inhibition as a promising approach for improving tubulin-based chemotherapy by promoting mitotic vulnerability in CRC.
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Date
1/1/2026
Student Status
Junior (Graduating in 2027)
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Type of presentation
Poster
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Program/Major
Molecular Genetics
College/School
College of Agriculture and Life Sciences
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Life Science