Abstract 4052: Evaluation of anti-tumor activity of SB-216, a novel potent tubulin inhibitor, in pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high mortality. It is the 4th leading cause of cancer-related death in the U.S. and has the lowest 5-year survival rate among all cancer types. One of the main hurdles for the treatment is limited effective chemotherapy and rapidly acquired resistance against it. Advanced PDAC research and various treatment options only showed minimal enhancement to the overall survival outcomes. Hence more effective drugs and therapies are in need for improving overall therapeutic outcomes for PDAC patients. Recently, we reported the discovery of a new generation of tubulin inhibitors (SB-216) that targets the colchicine binding site and serves as a potent anti-cancer agent for various cancer types. Here, we evaluated the in vitro effects of SB-216 on the PDAC cell lines in comparison with one of the first-line treatment paclitaxel. We also established luciferase labeled Mia PaCa-2 cell line, Mia PaCa-2-Luc, for live monitoring tumor progression and evaluating the anti-tumor effect in subcutaneous mouse models. The results showed that SB-216 effectively inhibited cell proliferation, colony formation, and cell migration dose-dependently at low nanomolar concentrations. Immunoblotting also confirmed SB-216 induced cell apoptosis in a dose-dependent manner. Cell cycle arrest assay confirmed that SB-216 can arrest cells in the G2/M phase. In vivo study suggested that SB-216 inhibited tumor growth significantly in Mia PaCa-2-Luc subcutaneous xenograft model with low toxicity. Our preclinical data demonstrated the potential of SB-216 to inhibit proliferation and induce apoptosis in PDAC cells, indicating a promising chemotherapy agent in treating PDAC. However, further evaluations are warranted in orthotopic and PDX tumor models for clinical significance. Citation Format: Rui Wang, Satyanarayana Pochampally, David Hamilton, Duane D. Miller, Wei Li. Evaluation of anti-tumor activity of SB-216, a novel potent tubulin inhibitor, in pancreatic cancer [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 4052.