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

Radwa Hablase; Ioannis Kyrou; Harpal Randeva; Emmanouil Karteris; Emmanouíl Karteris; Jayanta Chatterjee

doi:10.3390/cancers16112160

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

Radwa Hablase, Ioannis Kyrou, Harpal Randeva, Emmanouil Karteris, Emmanouíl Karteris, Jayanta Chatterjee

Cancers · 2024 · vol. 16(11) , pp. 2160 · doi:10.3390/cancers16112160 · PMID:38893278 · W4399388496

article OA: gold CC0 ⤵ 5 in-corpus citations

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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review examines mTOR pathway dysregulation in endometriosis and endometriosis-associated ovarian cancers, exploring its role in malignant transformation through interactions with driver gene mutations, environmental factors, and potential therapeutic targets.

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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.

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endometriosis

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[1] Aberrant PTEN expression in response to progesterone reduces endometriotic stromal cell apoptosis via openalex

[2] Activated AKT Pathway Promotes Establishment of Endometriosis via openalex

[3] Activation of mammalian target of rapamycin in postmenopausal ovarian endometriosis via openalex

[4] Activation of mammalian target of rapamycin in postmenopausal ovarian endometriosis via openalex

[5] Age‐dependent phenotypes of ovarian endometriomas via openalex

[6] A Revised Stem Cell Theory for the Pathogenesis of Endometriosis via openalex

[7] ARID1A protein expression is retained in ovarian endometriosis with ARID1A loss-of-function mutations: implication for the two-hit hypothesis via openalex

[8] Aromatase and endometriosis: estrogens play a role via openalex

[9] Association between endometriosis and cancer: A comprehensive review and a critical analysis of clinical and epidemiological evidence via openalex

[10] Association of Four Interleukin-8 Polymorphisms (-251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes via openalex

[11] Autophagy in endometriosis. via openalex

[12] <b>Ovarian atypical endometriosis: its close association with malignant epithelial tumours</b> via openalex

[13] Cancer-Associated Mutations in Endometriosis without Cancer via openalex

[14] Cancer risk after a hospital discharge diagnosis of endometriosis via openalex

[15] Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium via openalex

[16] Contents of Endometriotic Cysts, Especially the High Concentration of Free Iron, Are a Possible Cause of Carcinogenesis in the Cysts through the Iron-Induced Persistent Oxidative Stress via openalex

[17] Deep Infiltrating Endometriosis Malignant Invasion of Cervical Wall and Rectal Wall With Lynch Syndrome： A Rare Case Report and Review of Literature via openalex

[18] Dienogest enhances autophagy induction in endometriotic cells by impairing activation of AKT, ERK1/2, and mTOR via openalex

[19] Dienogest enhances autophagy induction in endometriotic cells by impairing activation of AKT, ERK1/2, and MTOR via openalex

[20] Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry via openalex

[21] Differential induction of autophagy by mTOR is associated with abnormal apoptosis in ovarian endometriotic cysts via openalex

[22] Differential regulation of Akt phosphorylation in endometriosis via openalex

[23] Distinct β-Catenin and PIK3CA Mutation Profiles in Endometriosis-Associated Ovarian Endometrioid and Clear Cell Carcinomas via openalex

[24] Dual inhibition of ERK1/2 and AKT pathways is required to suppress the growth and survival of endometriotic cells and lesions via openalex

[25] Effect of rapamycin on endometriosis in mice via openalex

[26] Endometrioid Carcinoma Arising from an Endometriosis-Associated Abdominal Wall Scar via openalex

[27] Endometriose und Malignom via openalex

[28] Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment via openalex

[29] Endometriosis after menopause: physiopathology and management of an uncommon condition via openalex

[30] Endometriosis and menopause—management strategies based on clinical scenarios via openalex

[31] Endometriosis and the estrogen threshold theory. Relation to surgical and medical treatment. via openalex

[32] Endometriosis-associated Malignancy via openalex

[33] Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy via openalex

[34] Endometriosis-Associated Ovarian Carcinomas: How PI3K/AKT/mTOR Pathway Affects Their Pathogenesis via openalex

[35] Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets—a narrative review via openalex

[36] Endometriosis classification, staging and reporting systems: a review on the road to a universally accepted endometriosis classification, via openalex

[37] Endometriosis - clinical approach based on histological findings. via openalex

[38] Endometriosis in Menopause—Renewed Attention on a Controversial Disease via openalex

[39] Endometriosis in the postmenopausal female: clinical presentation, imaging features, and management via openalex

[40] Endometriosis-Related Ovarian Cancers: Evidence for a Dichotomy in the Histogenesis of the Two Associated Histotypes via openalex

[41] Endometriosis‐related pathology: a discussion of selected uncommon benign, premalignant and malignant lesions via openalex

[42] Estrogen Production and Metabolism in Endometriosis via openalex

[43] Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis via openalex

[44] Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: a tissue microarray study via openalex

[45] Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma via openalex

[46] G protein–coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis via openalex

[47] Histologic Transformation of Benign Endometriosis to Early Epithelial Ovarian Cancer via openalex

[48] How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development via openalex

[49] Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis via openalex

[50] Hypoxia: The force of endometriosis via openalex

[51] <i>ARID1A</i> Mutations in Endometriosis-Associated Ovarian Carcinomas via openalex

[52] <i>In vitro</i> and <i>in vivo</i> effects of MK2206 and chloroquine combination therapy on endometriosis: autophagy may be required for regrowth of endometriosis via openalex

[53] Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis: potential implications for macrophages and follicle maturation via openalex

[54] Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma via openalex

[55] <i>PIK3CA</i> mutation is an early event in the development of endometriosis‐associated ovarian clear cell adenocarcinoma via openalex

[56] Local estrogen formation and its regulation in endometriosis via openalex

[57] Long-Term Follow-Up after Surgical Management for Atypical Endometriosis: A Series of Nine Cases via openalex

[58] Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation? via openalex

[59] Loss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell carcinoma. via openalex

[60] Loss of ARID1A Expression Is an Early Molecular Event in Tumor Progression From Ovarian Endometriotic Cyst to Clear Cell and Endometrioid Carcinoma via openalex

[61] Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. via openalex

[62] Malignant changes in endometriosis. via openalex

[63] Malignant Transformation and Associated Biomarkers of Ovarian Endometriosis: A Narrative Review via openalex

[64] Malignant Transformation of Postmenopausal Endometriosis: A Systematic Review of the Literature via openalex

[65] Molecular and Cellular Pathogenesis of Endometriosis via openalex

[66] Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives via openalex

[67] mTor Inhibitors for the Treatment of Endometriosis via openalex

[68] Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden via openalex

[69] New knowledge and insights about the malignant transformation of endometriosis via openalex

[70] Non‐hormonal targets underlying endometriosis: A focus on molecular mechanisms via openalex

[71] Ovarian cancer in endometriosis: an update on the clinical and molecular aspects via openalex

[72] Ovarian endometrioma—Risks factors of ovarian cancer development via openalex

[73] Ovarian Endometriosis Associated with Ovarian Carcinoma: A Clinicopathological and Immunohistochemical Study via openalex

[74] Parametrial and rectovaginal adenocarcinoma arising from endometriosis via openalex

[75] Parametrial and rectovaginal adenocarcinoma arising from endometriosis via openalex

[76] (Partial) Loss of BAF250a (<i>ARID1A</i>) in rectovaginal deep-infiltrating endometriosis, endometriomas and involved pelvic sentinel lymph nodes via openalex

[77] Pathogenesis and pathophysiology of endometriosis via openalex

[78] Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity via openalex

[79] Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review via openalex

[80] PI3K/AKT pathway is altered in the endometriosis patient’s endometrium and presents differences according to severity stage via openalex

[81] Postmenopausal endometriosis: drawing a clearer clinical picture via openalex

[82] Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms via openalex

[83] Prognostic Importance of Hyperplasia and Atypia in Endometriosis via openalex

[84] Prostaglandin E2 Stimulates Aromatase Expression in Endometriosis-Derived Stromal Cells via openalex

[85] Prostaglandin E<sub>2</sub>Stimulates Aromatase Expression in Endometriosis-Derived Stromal Cells<sup>1</sup> via openalex

[86] Relationship between adenomyosis and endometriosis; Different phenotypes of a single disease? via openalex

[87] Revised American Society for Reproductive Medicine classification of endometriosis: 1996 via openalex

[88] Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review via openalex

[89] Role of AMPK/mTOR, mitochondria, and ROS in the pathogenesis of endometriosis via openalex

[90] Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer via openalex

[91] Symptomatic endometriosis developing several years after menopause in the absence of increased circulating estrogen concentrations: a systematic review and seven case reports via openalex

[92] The <i>ARID1A</i> pathway in ovarian clear cell and endometrioid carcinoma, contiguous endometriosis, and benign endometriosis via openalex

[93] The missed disease? Endometriosis as an example of ‘undone science’ via openalex

[94] THE PATHOGENESIS OF ENDOMETRIOSIS via openalex

[95] The presence of KRAS, PPP2R1A and ARID1A mutations in 101 Chinese samples with ovarian endometriosis via openalex

[96] The relation between endometrioma and ovarian cancer via openalex

[97] The relation between endometriosis and ovarian cancer – a review via openalex

[98] Transactivation of Steroidogenic Acute Regulatory Protein in Human Endometriotic Stromal Cells Is Mediated by the Prostaglandin EP2 Receptor via openalex

[99] Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu via openalex

[100] Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma. via openalex