An update on Mullerian-inhibiting substance: its potential application against ovarian cancer

Each year, similar to 25 000 women are newly diagnosed with ovarian cancer in the USA. The vast majority (>90%) of cases are of epithelial origin. This highly lethal cancer carries a mortality rate of >50% and a high risk of recurrence after conventional, first-line chemotherapy. Mullerian-inhibiting substance (MIS) is a gonadal hormone that causes regression of the Mullerian ducts. A series of studies have demonstrated that MIS also has multiple extra-Mullerian functions including inhibition of epithelial ovarian cancer cells in vitro and in vivo. Accumulating evidence has shown that many human cancers are organized hierarchically and contain a small population of cancer stem cells (CSCs) that are inherently resistant to common chemotherapy and radiation therapy. The effect of MIS on ovarian CSC seems to be particularly useful in rescuing ovarian cancer patients with resistance to conventional treatment. Based on recent studies evaluating MIS, this review updates our current understanding of the molecular genetic aspects of MIS, its pathophysiology, as well as its potential to treat chemoresistant epithelial ovarian cancer.