4.7 Review

Emerging Drug Targets for Endometriosis

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Review Immunology

A review of the effects of estrogen and epithelial-mesenchymal transformation on intrauterine adhesion and endometriosis

He-yu Liu et al.

Summary: Uterus transplantation is an option for infertility treatment. This review emphasizes the role of estrogen and epithelial-mesenchymal transition (EMT) in the pathogenesis and treatment of endometrial disorders. It also discusses the regulatory relationship between estrogen and EMT and explores potential therapeutic targets and drugs for endometrial disorders.

TRANSPLANT IMMUNOLOGY (2023)

Article Obstetrics & Gynecology

Silencing of circ_0007299 suppresses proliferation, migration, and invasiveness and promotes apoptosis of ectopic endometrial stromal cells in endometriosis via miR-424-5p-dependent modulation of CREB1

Haiyan Mao et al.

Summary: Our study demonstrates that circ_0007299 silencing inhibits the proliferation, invasiveness, and motility, and promotes apoptosis of ectopic endometrial stromal cells (ESCs), at least in part, through the miR-424-5p-dependent modulation of CREB1.

ARCHIVES OF GYNECOLOGY AND OBSTETRICS (2023)

Article Endocrinology & Metabolism

Hormonal treatments for endometriosis: The endocrine background

Silvia Vannuccini et al.

Summary: Endometriosis is a chronic uterine disorder that affects women's health, and hormonal drugs are the main medical treatment used to manage the disease based on endocrine and inflammatory changes. The key events causing pain and infertility are estrogen-dependency and progesterone-resistance. Current treatments aim to inhibit menstruation, block the hypothalamus-pituitary-ovary axis, and control the progression of endometriotic implants.

REVIEWS IN ENDOCRINE & METABOLIC DISORDERS (2022)

Article Pathology

Effects of metformin, letrozole and atorvastatin on inflammation and apoptosis in experimental peritoneal and ovarian endometriosis in the rat

Tansel Sapmaz et al.

Summary: This study investigated the effects of metformin, letrozole, and atorvastatin on experimentally induced ovarian and peritoneal endometriosis in rat models. All treatment groups showed a decrease in cell proliferation and an increase in cell apoptosis. Additionally, the treatment groups exhibited a significant reduction in inflammation compared to the untreated group.

PATHOLOGY RESEARCH AND PRACTICE (2022)

Article Endocrinology & Metabolism

SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell via Balancing ERa and PR Signals

Yi-Kong Lin et al.

Summary: This study suggests that the interaction between inflammation and endocrine imbalance plays a significant role in the development of endometriosis (EMS). SCM-198 inhibits the progression of EMS by regulating the inflammation-endocrine-autophagy axis.

FRONTIERS IN ENDOCRINOLOGY (2022)

Review Biochemistry & Molecular Biology

An Update on the Multifaceted Role of NF-kappaB in Endometriosis

Yuanmeng Liu et al.

Summary: This review discusses the role of NF-KB signaling in endometriosis and its regulation by various factors. It provides an update on the effects of NF-KB on endometriotic cells, peritoneal macrophages, and endometriosis-related symptoms, and summarizes potential drugs for targeting NF-KB.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2022)

Article Obstetrics & Gynecology

Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study

Yutaka Osuga et al.

Summary: This study evaluated the efficacy and safety of relugolix in treating endometriosis-associated pain, showing that oral administration of relugolix alleviated pain in a dose-response manner and was generally well tolerated. Relugolix demonstrated efficacy and safety comparable to leuprorelin, another treatment option.

FERTILITY AND STERILITY (2021)

Article Toxicology

Pyrvinium pamoate induces in-vitro suppression of IL-6 and IL-8 produced by human endometriotic stromal cells

Amin Karamian et al.

Summary: Endometriosis is a chronic inflammatory disease with a prevalence of around 10-15% among reproductive-age women. High levels of IL-6 and IL-8 have been found in the peritoneal fluid of women with this disease, and are involved in its pathogenesis. The compound pyrvinium pamoate shows potential in suppressing the mRNA gene expression and secretion of IL-6 and IL-8 in human endometriotic stromal cells, but further research is needed before clinical application.

HUMAN & EXPERIMENTAL TOXICOLOGY (2021)

Review Obstetrics & Gynecology

Use of dopamine agonists to target angiogenesis in women with endometriosis

Nuria Pellicer et al.

Summary: Endometriosis requires medical management during a woman's reproductive years, with most treatments aiming to create a hypoestrogenic environment. Targeting angiogenesis using dopamine agonists (DAs) is a promising strategy for reducing lesion size and pain in endometriosis by downregulating proangiogenic pathways and upregulating antiangiogenic pathways.

HUMAN REPRODUCTION (2021)

Review Biochemistry & Molecular Biology

Pathogenesis of Endometriosis: New Insights into Prospective Therapies

Radhika Kapoor et al.

Summary: Endometriosis is a female reproductive disorder with a low rate of early detection, the treatment mainly involves hormone therapies, thus there is a need to study alternative strategies that are more effective and have fewer side effects.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Review Biochemistry & Molecular Biology

GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis?

Jacques Donnez et al.

Summary: Oral gonadotropin-releasing hormone (GnRH) antagonists have shown effectiveness in managing endometriosis-associated symptoms, especially in patients who do not respond well to traditional treatments. Research needs to take into account the different phenotypes of the disease and propose novel treatment algorithms in order to improve management strategies.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Review Biochemistry & Molecular Biology

New Therapeutics in Endometriosis: A Review of Hormonal, Non-Hormonal, and Non-Coding RNA Treatments

Geraldine Brichant et al.

Summary: Endometriosis is a chronic inflammatory disease causing pain and infertility, with current treatments focusing on medication and surgery. Medical treatments have not been able to cure the disease, highlighting the need for new biomedical targets. Non-coding RNAs are emerging as potential key players in the treatment of endometriosis and other human diseases like cancer.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Chemistry, Medicinal

Ursolic Acid Inhibits Collective Cell Migration and Promotes JNK-Dependent Lysosomal Associated Cell Death in Glioblastoma Multiforme Cells

Gillian E. Conway et al.

Summary: The study demonstrates that ursolic acid rapidly induces lysosomal-associated cell death and inhibits cell migration in glioblastoma, indicating a potential therapeutic target in cancer treatment.

PHARMACEUTICALS (2021)

Article Medicine, General & Internal

Endometriosis is a chronic systemic disease: clinical challenges and novel innovations

Hugh S Taylor et al.

LANCET (2021)

Article Oncology

miR-143-3p inhibits endometriotic stromal cell proliferation and invasion by inactivating autophagy in endometriosis

Hong Yang et al.

Summary: miR-143-3p inhibits the progression of endometriosis, potentially serving as a novel target for therapeutic agents against the disease.

MOLECULAR MEDICINE REPORTS (2021)

Article Obstetrics & Gynecology

Disturbed progesterone signalling in an advanced preclinical model of endometriosis

Fereshteh Esfandiari et al.

Summary: Human endometriosis organoids were established from biopsies of women with and without endometriosis and showed aberrant expressions of endometriosis-related genes compared to control endometrium organoids. These endometriosis organoids exhibited a decreased response to progesterone, with significant downregulation of Progesterone receptor B (PRB) gene expression. Epigenetic mechanisms such as DNA hypermethylation at the PRB promoter were detected in eutopic but not ectopic organoids, implying other mechanisms like histone modifications and microRNAs may be responsible for PRB downregulation in ectopic organoids. Endometriosis organoids serve as valuable preclinical models for investigating the molecular mechanisms of endometriosis-associated progesterone resistance.

REPRODUCTIVE BIOMEDICINE ONLINE (2021)

Review Medicine, General & Internal

Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review

Jacques Donnez et al.

Summary: Oral contraceptive pills and progestogens are effective in treating most women with endometriosis, but alternative options are needed for those who fail treatment due to progesterone resistance or intolerance. Effective long-term oral treatment is necessary for managing endometriosis symptoms while minimizing side effects. Research on progesterone resistance and new treatment options should be further explored.

JOURNAL OF CLINICAL MEDICINE (2021)

Article Biochemistry & Molecular Biology

A Reassessment of the Therapeutic Potential of a Dopamine Receptor 2 Agonist (D2-AG) in Endometriosis by Comparison against a Standardized Antiangiogenic Treatment

Miguel A. Tejada et al.

Summary: Studies in mouse models have shown that D2-ags and anti-VEGF compounds can significantly reduce the size and vascular density of endometriosis lesions, opening up possibilities for future application in human treatment.

BIOMEDICINES (2021)

Article Cell Biology

Upregulation of fibroblast growth factor 2 contributes to endometriosis through SPRYs/DUSP6/ERK signaling pathway

Xiaoyan Yu et al.

Summary: The study indicates that upregulation of FGF2 in endometriosis patients may promote the disease progression by affecting the regulation of the SPRYs/DUSP6/ERK signaling pathway.

ACTA HISTOCHEMICA (2021)

Review Biochemistry & Molecular Biology

Can Endometriosis-Related Oxidative Stress Pave the Way for New Treatment Targets?

Luciana Cacciottola et al.

Summary: Endometriosis is a complex disease with chronic inflammation, immune system dysregulation, and oxidative stress playing important roles in its development. Targeting oxidative stress appears to be a promising strategy to curb disease progression and alleviate symptoms of chronic pain and infertility. Further research is needed to develop effective therapeutic strategies for clinical application.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Obstetrics & Gynecology

The pro-inflammatory and anti-inflammatory role of hyaluronic acid in endometriosis

Pei-Hsiu Yu et al.

Summary: The study demonstrated that the use of hyaluronic acid in endometriosis may induce both proinflammatory and anti-inflammatory responses. Elevated COX-2 expression and reduced endometriosis lesion size and COX-2 expression score were observed after hyaluronic acid treatment in in vivo and in vitro models. The findings suggest that hyaluronic acid may initiate an acute proinflammatory response followed by a chronic anti-inflammatory reaction in the development of endometriosis.

TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY (2021)

Review Biochemistry & Molecular Biology

Endometriosis: Etiology, pathobiology, and therapeutic prospects

Philippa T. K. Saunders et al.

Summary: Endometriosis is a common condition associated with infertility that causes chronic pain in women. The exact cause and natural history are still uncertain, but hormonal, neurological, and immunological factors are believed to play a role in the development of symptoms. Current interventions have limited efficacy with high rates of symptom recurrence.
Review Biochemistry & Molecular Biology

Curcumin and Endometriosis

Alexandre Vallee et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Review Endocrinology & Metabolism

Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

Chloe Hogg et al.

FRONTIERS IN ENDOCRINOLOGY (2020)

Review Medicine, General & Internal

Epithelial-Mesenchymal Transition in Endometriosis-When Does It Happen?

Lutz Konrad et al.

JOURNAL OF CLINICAL MEDICINE (2020)

Article Obstetrics & Gynecology

Health-Related Quality of Life Improvements in Patients With Endometriosis Treated With Elagolix

Hugh S. Taylor et al.

OBSTETRICS AND GYNECOLOGY (2020)

Article Immunology

Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis

Ahmed A. El-Zayadi et al.

IMMUNOLOGIC RESEARCH (2020)

Article Health Care Sciences & Services

Real-World Characterization of Women with Diagnosed Endometriosis Initiating Therapy with Elagolix Using a US Claims Database

Eric S. Surrey et al.

CLINICOECONOMICS AND OUTCOMES RESEARCH (2020)

Review Obstetrics & Gynecology

Endometriosis and nuclear receptors

Bahar D. Yilmaz et al.

HUMAN REPRODUCTION UPDATE (2019)

Review Endocrinology & Metabolism

Endometriosis

Serdar E. Bulun et al.

ENDOCRINE REVIEWS (2019)

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Naringenin ameliorates progression of endometriosis by modulating Nrf2/Keap1/HO1 axis and inducing apoptosis in rats

Radhika Kapoor et al.

JOURNAL OF NUTRITIONAL BIOCHEMISTRY (2019)

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Different mutation profiles between epithelium and stroma in endometriosis and normal endometrium

Kazuaki Suda et al.

HUMAN REPRODUCTION (2019)

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Pathogenesis of endometriosis: the genetic/epigenetic theory

Philippe R. Koninckx et al.

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Cyclooxygenase-2 in Endometriosis

Zhen-Zhen Lai et al.

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Nobiletin alleviates endometriosis via down-regulating NF-κB activity in endometriosis mouse model

Xin Wei et al.

BIOSCIENCE REPORTS (2018)

Review Pharmacology & Pharmacy

Current and emerging treatment options for endometriosis

Simone Ferrero et al.

EXPERT OPINION ON PHARMACOTHERAPY (2018)

Editorial Material Obstetrics & Gynecology

Are combined hormonal contraceptives the neglected treatment for symptomatic endometriosis?

Paolo Vercellini

FERTILITY AND STERILITY (2018)

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Invasion of human deep nodular endometriotic lesions is associated with collective cell migration and nerve development

Javier Garcia-Solares et al.

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Article Endocrinology & Metabolism

Progesterone Receptor Status Predicts Response to Progestin Therapy in Endometriosis

Valerie A. Flores et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2018)

Article Obstetrics & Gynecology

Partial suppression of estradiol: a new strategy in endometriosis management?

Jacques Donnez et al.

FERTILITY AND STERILITY (2017)

Article Psychology, Clinical

The burden of endometriosis symptoms on health-related quality of life in women in the United States: a cross-sectional study

Ahmed M. Soliman et al.

JOURNAL OF PSYCHOSOMATIC OBSTETRICS & GYNECOLOGY (2017)

Article Medicine, General & Internal

Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist

H. S. Taylor et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Review Obstetrics & Gynecology

Progesterone resistance in endometriosis: origins, consequences and interventions

Bansari G. Patel et al.

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Challenges in the development of novel therapeutic strategies for treatment of endometriosis

Arne Vanhie et al.

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Oxidative stress in the pelvic cavity and its role in the pathogenesis of endometriosis

Jacques Donnez et al.

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Review Obstetrics & Gynecology

Estrogen-progestins and progestins for the management of endometriosis

Paolo Vercellini et al.

FERTILITY AND STERILITY (2016)

Review Obstetrics & Gynecology

The direct and indirect costs associated with endometriosis: a systematic literature review

Ahmed M. Soliman et al.

HUMAN REPRODUCTION (2016)

Review Chemistry, Medicinal

Influencing COX-2 Activity by COX Related Pathways in Inflammation and Cancer

Tingting Yu et al.

MINI-REVIEWS IN MEDICINAL CHEMISTRY (2016)

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Sunitinib as an anti-endometriotic agent

Manal A. Abbas et al.

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES (2013)

Article Obstetrics & Gynecology

Nerve fiber density in deep nodular endometriotic lesions induced in a baboon experimental model

Olivier Donnez et al.

FERTILITY AND STERILITY (2013)

Article Developmental Biology

Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

Carla N. Olivares et al.

REPRODUCTION (2013)

Article Obstetrics & Gynecology

The Efficacy of Bevacizumab, Sorafenib, and Retinoic Acid on Rat Endometriosis Model

Hatice Ozer et al.

REPRODUCTIVE SCIENCES (2013)

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The mTOR/AKT Inhibitor Temsirolimus Prevents Deep Infiltrating Endometriosis in Mice

Mahaut Leconte et al.

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Antiproliferative Effects of Cannabinoid Agonists on Deep Infiltrating Endometriosis

Mahaut Leconte et al.

AMERICAN JOURNAL OF PATHOLOGY (2010)

Editorial Material Obstetrics & Gynecology

More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis

Eugenia Pittaluga et al.

FERTILITY AND STERILITY (2010)

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Endometriosis.

Linda C. Giudice

NEW ENGLAND JOURNAL OF MEDICINE (2010)

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17β-Hydroxysteroid Dehydrogenase-2 Deficiency and Progesterone Resistance in Endometriosis

Serdar Bulun et al.

SEMINARS IN REPRODUCTIVE MEDICINE (2010)

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Epigenetics of endometriosis

Sun-Wei Guo

MOLECULAR HUMAN REPRODUCTION (2009)

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Anti-TNF-α treatment for deep endometriosis-associated pain:: a randomized placebo-controlled trial

P. R. Koninckx et al.

HUMAN REPRODUCTION (2008)

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Activation of mammalian target of rapamycin in postmenopausal ovarian endometriosis

T. Yagyu et al.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER (2006)

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Reactive oxygen species-induced activation of the MAP kinase signaling pathways

James A. McCubrey et al.

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Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms

T Parasassi et al.

CELL DEATH AND DIFFERENTIATION (2005)

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Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis

Y Wu et al.

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY (2005)

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Distinct regulation of cyclooxygenase-2 by interleukin-1 beta in normal and endometriotic stromal cells

MH Wu et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2005)

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Iron overload in the peritoneal cavity of women with pelvic endometriosis

A Van Langendonckt et al.

FERTILITY AND STERILITY (2002)

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Was Sampson wrong?

DB Redwine

FERTILITY AND STERILITY (2002)

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Leflunomide: mode of action in the treatment of rheumatoid arthritis

FC Breedveld et al.

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