Abstract 1047: Combinatorial anticancer therapy strategy using a pan-class I glucose transporter inhibitor with chemotherapy and target drugs in vitro and in vivo (2022)

Abstract Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer, accounting for 84% of all lung cancer diagnoses. While there are current standard treatments for NSCLC, these treatments may cause severe side effects, drug resistance, or lead to ineffective treatment, recurrence of the cancer, and death. It has been shown that most cancer types are “addicted” to glucose, and are sensitive and vulnerable to glucose deprivation, making the inhibition of glucose transport into these cells an attractive anticancer strategy. DRB18 is a small molecule proprietary compound that has been shown to target and inhibit class I glucose transporters (GLUTs, GLUT1-4), which are responsible for the uptake of glucose into cells, particularly these types of cancer cells. DRB18 has been shown to be effective in inhibiting cancer cell growth in vitro and in vivo without noticeable side effects.1 While this may be a promising anticancer therapy by itself, combining DRB18 with another anticancer drug that has a totally different anticancer mechanism should substantially increase the efficacy of the treatment while potentially minimizing the rate of resistance and recurrence of the cancer without increasing unwanted side effects. This research focuses on combining DRB18 with FDA-approved target drugs Trametinib and Brigatinib, the FDA-approved chemotherapy drug Paclitaxel, and a glutamine transporter inhibitor (V-9302). Thus, the treatment groups are vehicle, each of the previously mentioned drugs alone, as well as DRB18+Trametinib, DRB18+Brigatinib, DRB18+Paclitaxel, and DRB18+V-9302. This study tests the hypothesis that, due to their different anticancer mechanisms, the combination of DRB18 with these anticancer drugs will have a synergistic anticancer effect. Preliminary in vitro data and an in vivo pilot tumor study in nude mice, using human NSCLC A549 cells, have shown the improved anticancer efficacy of the combinatorial approach by further reducing tumor growth when compared with single drug treatment. The results of a larger nude mouse study, as well as basic mechanistic studies in vitro, that are currently underway will be presented later at the AACR meeting. This combination therapy has great therapeutic implications and the potential to benefit cancer patients for decades to come. 1. Shriwas P, Roberts D, Li Y, Wang L, Qian Y, Bergmeier S, Hines J, Adhicary S, Nielsen C, &amp; Chen X. (2021). A small molecule pan-class I glucose transporter inhibitor reduces cancer cell proliferation in vitro and tumor growth in vivo by targeting glucose-based metabolism. Cancer and Metabolism, 9 (14). Citation Format: Lindsey M. Bachmann, Pratik Shriwas, Ryan A. Ward, Liyi Wang, Stephen C. Bergmeier, Yunsheng Li, Xiaozhuo Chen. Combinatorial anticancer therapy strategy using a pan-class I glucose transporter inhibitor with chemotherapy and target drugs in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1047.