Targeting E-cadherin expression with small molecules for digestive cancer treatment

Digestive system cancers, mainly including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer, are major public health problems and lead to serious cancer-related deaths worldwide. Clinically, treatment strategies of these cancers include surgery, chemotherapy, and immunotherapy. Although successful resection and chemotherapeutic drugs have improved the treatment level, the survival rate of patients with advanced digestive system cancers remains still low primarily due to tumor metastasis. E-cadherin, the prototypical member of the type-1 classical cadherins, has been characrized as an important molecule in epithelial-mesenchymal transition (EMT) process. Loss of E-cadherin is able to induce EMT process, which is associated with cancer stem cells and drug resistance in human cancer. Therefore, restoring E-cadherin could be a useful strategy for reversal of EMT and overcoming drug resistance. In this review, we describe pharmacological small molecules targeting E-cadherin expression for the treatment of digestive system cancers, which have emerged in the recent 5 years. We hope these compounds could be potentially used for treating cancer in the near future.