γ-Secretase inhibitors for breast cancer and hepatocellular carcinoma: From mechanism to treatment

The γ-secretase complex is a key hydrolase for many type 1 transmembrane proteins. It is very important for activation of the Notch receptor and regulation of target-gene transcription. Abnormal activation and expression of the Notch pathway are closely related to the occurrence and development of many tumor types, including breast cancer and liver cancer. In this review, we elaborated on the basic situation of γ-secretase complex and the biological function and role of γ-secretase in APP and Notch signal pathway are described in detail. Subsequently, all currently known γ-secretase inhibitors and γ-secretase modulators are listed and their mechanism of action, value of IC50, chemical structure and current research stage are summarized. Next, the selection presented the treatment progress of γ-secretase inhibitors in breast cancer and hepatocellular carcinoma in the past five years. Finally, the mechanism of action of γ-secretase-mediated breast cancer and hepatocellular carcinoma and the advantages and disadvantages of γ-secretase inhibitors are discussed, and the concept of further research is proposed.