The “Road” to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review

Simple Summary: Ovarian cancer is the eighth most common cancer among women globally and 207,000 women die every year, whereas endometriosis affects around 10% of women of reproductive age. Endometriosis-associated ovarian cancers (EAOCs) frequently arise from ectopic endometrium (i.e., the presence of endometrial/stromal cells outside the uterine cavity) in the ovary. Over the past decades, there has been an increasing volume of evidence to suggest that signalling centred around the mechanistic target of rapamycin (mTOR) plays an important role in cellular functions such as proliferation, survival, and autophagy. This review summarizes the current landscape of mTOR signalling in these gynaecological malignancies and the emerging therapeutic options. Abstract: Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR dysregulation in endometriosis and EAOCs, investigating cancer driver gene mutations and their potential interaction with the mTOR pathway. Additionally, we explore the complex pathogenesis of transformation, considering environmental, hormonal, and epigenetic factors. We then discuss postmenopausal endometriosis pathogenesis and propensity for malignant transformation. Finally, we summarize the current advancements in mTOR-targeted therapeutics for endometriosis and EAOCs.