Repurposing metformin for choriocarcinoma: targeting the AMPK/mTOR pathway

Gestational trophoblastic neoplasia (GTN) includes a unique group of human neoplastic diseases that derive from fetal trophoblastic tissues. Choriocarcinoma is the most aggressive type of GTN, and patients tend to develop early systemic metastases. It can be either gestational or non-gestational in origin. Although most patients with gestational trophoblastic neoplasia are cured by chemotherapy and tumor resection, some patients suffer from metastatic diseases that are refractory to conventional chemotherapy. Therefore, new therapeutic regimens are needed to reduce the toxic effects associated with current chemotherapy and to salvage the occasional non-operable patients with recurrent and chemo-resistant disease. Until the fundamental biology of gestational trophoblastic neoplasia becomes more clearly understood, development of a new treatment will remain empirical. It has been shown that the antidiabetic metformin, by its antiproliferative effect, can reduce the proliferation and metastasis of choriocarcinoma. However, the fundamental cellular and molecular mechanisms of metformin in treating gestational choriocarcinoma are not fully elucidated. Therefore, this review will briefly summarize the recent advances in understanding the molecular mechanisms of metformin in gestational choriocarcinoma.