Abstract Background: Colorectal cancer (CRC) is the third most frequent cancer in the United States, and it is linked to poor outcomes. NAD(P)H: Quinone Oxidoreductase 1 (NQO1) is an enzyme that has been demonstrated to help in chemoprotection in CRC. The purpose of this meta-analysis is to investigate the relationship between NQO1 C609T polymorphisms and the risk of CRC. The study also investigates the binding ability and efficacy of BBI 608 against NQO1 in CRC using molecular docking. Methods: Google Scholar, PubMed, and Web of Science were utilized for bibliographic searches. The NQO1 C609T analysis included 18 studies. Data was collected and then calculated using the pooled odds ratio (OR) with a 95% confidence interval. Molecular docking, Western Blot, and QRT-PCR were utilized to determine BBI 608 and NQO1's molecular function. Results: The NQO1 polymorphism was significantly associated with CRC risk (OR = 1.19, 95% CI = 1.06-1.34, p 0.001). A stratified examination by ethnicity found a significant connection between the NQO1 polymorphism and CRC risk (TT + CT vs. CC: OR = 1.17, 95% CI = 1.08-1.27, p 0.001). This study demonstrates that the NQO1 C609T polymorphism increases the risk of CRC in both Asians and Caucasians. Computational techniques were used to explore the molecular characteristics of BBI 608 (an NQO1 inhibitor) and determine the precise mechanism of NQO1 in CRC. This study provides a deep insight into the interplay between NQO1 and BBI 608, as well as its implications for CRC treatment. In vitro experiments were conducted to supplement this computational analysis. BBI 608 causes dose-dependent cytotoxicity in CRC cell lines. BBI 608 treatment significantly (p 0.001) decreased NQO1 expression at protein and RNA levels in both CRC cell lines (HCT116 and RKO). Conclusion: According to a meta-analysis and computational technique, NQO1 is a valid biomarker and possible molecular target in CRC. In vitro studies revealed that suppressing NQO1 with BBI 608 reduced cell growth in both CRC cell lines. Knockout, overexpression, and site-directed mutagenesis are necessary for a deeper understanding of BBI 608-targeted NQO1 and its amino acid residues. Citation Format: Chaithanya Ganji, Raasil R. Basha, Karthikeya Ganji, Mehmet Akce, Bassel F. El-Rayes. NAD(P)H: Quinone oxidoreductase 1 (NQO1): Is it a potential molecular target in colorectal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7088.
Ganji et al. (Fri,) studied this question.