ESR1 and endometrial cancer: In addition to direct activation by ER, both the PI3K/Akt/mTOR pathway and a second pathway that is commonly altered in endometrial cancer [11], the receptor tyrosine kinase (RTK)/RAS/β-catenin (CTNNB1) pathway, can activate CDK4/6, leading to cell cycle progression via retinoblastoma (RB1), therefore causing cell proliferation and growth [24,25].