Small Molecule Chemosensitizing Agents: Polo-Like Kinase 1 (Plk1), BRAF and Janus Kinase (JAK) Inhibitors

Abstract

Abstract The overexpression of ATP-binding cassette (ABC) drug transporters contributes significantly to the development of multidrug resistance (MDR) phenotype in cancer cells. Transient downregulation or direct inhibition of the efflux function of ABC drug transporters by synthetic compounds is thought to be an efficient way to restore chemosensitivity in MDR cancer cells. Over the past few decades, a tremendous amount of effort has been spent on developing new modulators of ABC drug transporters suitable for use in clinical practice, but without success till date. Alternatively, repositioning of approved drugs to resensitize MDR cancer cells to conventional chemotherapeutic agents is more efficient and safer. Recent studies indicate that some protein kinase inhibitors can potentially be used as modulators in combination therapy for cancer. In this chapter, we provide a summary of some of the major findings comparing ABC drug transporter interactions with inhibitors of polo-like kinase 1, BRAF, and Janus kinase.