Bruton's Tyrosine Kinase (BTK) Inhibitors as Sensitizing Agents for Cancer Chemotherapy

Abstract

Abstract The urgent unmet need of improving the outcomes of cancer patients is to develop novel treatment strategies that can reduce the systemic toxicity of chemotherapy and overcome the multiple drug resistance (MDR). Developing effective combination treatment regimens is an ideal approach to improve the efficiency of chemotherapy. Bruton's tyrosine kinase (BTK) is a key component of the B-cell receptor (BCR) signaling pathway and plays an essential role in B-cell maturation and lymphomagenesis. The development of BTK inhibitors and their application in clinic represent the major advance in the treatment of hematological malignancies. Recently, extensive studies have demonstrated that the aberrant activation of the BTK signaling pathway has been involved in MDR. Targeting the BTK signaling pathway could sensitize the cancer cells resistant to various chemotherapy drugs including paclitaxel, cisplatin, doxorubicin, proteasome inhibitors, Bcl-2 antagonists, and HDAC inhibitors. The combination treatment strategies using the BTK inhibitor, ibrutinib, and other chemotherapy agents have been proven effective in targeting resistant cell lines. Some of the combination treatment regimens are currently tested in clinical trials. In this chapter, the mechanisms, applications, as well as the efficacy of BTK inhibitors acting as sensitizing agents in cancer chemotherapy are discussed.