Inhibition of MST1/2 Kinases of the Hippo Signaling Pathway Enhances Antitumor Chemotherapy in Hematological Cancers.

Abstract

Primary drug resistance of tumor cells or resistance acquired during treatment is among the main factors that significantly limit the efficacy of antitumor chemotherapy, along with severe side effects depending on the drug dose. To increase the efficacy, chemotherapeutics can be used in combination with substances that modulate the functions of cell signaling pathways. In this work, the substance XMU-MP-1, an inhibitor of key MST1/2 kinases of the Hippo signaling pathway, was shown to enhance the antitumor activity of two genotoxic chemotherapeutics, etoposide and cisplatin, against Namalwa Burkitt's B-cell lymphoma cells. XMU-MP-1 increased the cytotoxicity of the agents and significantly reduced their CTD₅₀. The drug efficacy is therefore possible to increase significantly, and a therapeutic effect might be achieved at a lower drug concentration to reduce the likelihood of life-threatening side effects.