Advancement in preclinical development of cancer treatment agents through modulation of Rac1: From EHop-016 to natural products

Rac1 belongs to the Rac subfamily under the Rho family of GTPases. As an effector of K-Ras protein encoded by the KRAS gene, Rac1 activation plays a key role in KRAS-driven cancer development and is largely involved in the promotion of cell migration and chemoresistance in pancreatic cancer. Evidence has indicated that pancreas-specific knockdown of Rac1 may prevent disease progression, while pharmacological inhibition of Rac1 can exert strong anti-cancer effects. In this review, we have discussed the relationship between Rac1 and neoplastic development, whereas different treatment schemes on pancreatic cancer through modulation of Rac1 during chemotherapy will be emphasized. Furthermore, we elaborated on contemporary studies of the Rac1 inhibitor EHop-016 and related compounds that have shown anti-tumor capability in preclinical models and their potential clinical applications. Exploration on the therapeutic prospect of phytochemicals derived from natural products capable of inhibiting cancer cell growth and disease progression by modulating Rac1 has been envisaged. Lastly, the complex correlation between Rac1 signaling and autophagy during treatment of pancreatic cancer by the novel phytochemical isoliquiritigenin would be introduced.