KDM1A and mTOR inhibition is a novel therapeutic combination for the treatment of endometrial cancer

Abstract

Endometrial cancer (EC) is the sixth most common cancer in women. Annually 50,230 new cases are being diagnosed with 8590 deaths estimated in USA. Currently, advanced endometrial cancer has limited therapeutic options and new therapies are urgently needed. The common risk factors include exposure to high levels of estrogen and obesity and alterations in genetic and epigenetic factors. The lysine-specific demethylase-1 (KDM1A/LSD1) regulates gene expression programs by changing the epigenetic histone marks at the gene promoters. Emerging studies provided the evidence that KDM1A is overexpressed in EC and KDM1A activates mTOR signaling, and PI3K/Akt pathway increases KDM1A expression. Recent clinical studies demonstrated that mTOR inhibitors has encouraging activity against EC patients. We hypothesize that inhibition of KDM1A could sensitize EC to mTOR inhibitor therapy.