Promising natural products targeting protein tyrosine phosphatase SHP2 for cancer therapy

Abstract The development of Src homology‐2 domain containing protein tyrosine phosphatase‐2 (SHP2) inhibitors is a hot spot in the research and development of antitumor drugs, which may induce immunomodulatory effects in the tumor microenvironment and participate in anti‐tumor immune responses. To date, several SHP2 inhibitors have made remarkable progress and entered clinical trials for the treatment of patients with advanced solid tumors. Multiple compounds derived from natural products have been proved to influence tumor cell proliferation, apoptosis, migration and other cellular functions, modulate cell cycle and immune cell activation by regulating the function of SHP2 and its mutants. However, there is a paucity of information about their diversity, biochemistry, and therapeutic potential of targeting SHP2 in tumors. This review will provide the structure, classification, inhibitory activities, experimental models, and antitumor effects of the natural products. Notably, this review summarizes recent advance in the efficacy and pharmacological mechanism of natural products targeting SHP2 in inhibiting the various signaling pathways that regulate different cancers and thus pave the way for further development of anticancer drugs targeting SHP2.