Developmental Origins and Emerging Therapeutic Opportunities for Uterine Fibroids

Dear Colleagues,

We are pleased to invite you to publish your research results in a new Special Issue concerning developmental origins and emerging therapeutic opportunities for uterine fibroids (UFs). A large number of unclear UF-related issues make this area the focus of intensive investigational activity.

It is currently known that uterine fibroids are the most common benign tumors occurring in women of reproductive age. The occurrence of UFs is estimated at about 25% to as much as 70% depending on different risk factors, where ethnicity and age are believed to be the most important ones. Abnormal uterine bleeding, pelvic pain, voiding issues or constipation, and reproductive dysfunction are some of the most common UF-related symptoms.

UFs consist of uterine smooth muscle placed in a large amount of disorganized extracellular matrices. Numerous pathways have been confirmed to contribute to UF development and growth. Genetic research has demonstrated that UFs are monoclonal tumors originating from the myometrial stem cells. Recently published results have shown that specific mutations within the gene coding the mediator complex subunit 12 (MED12) have been found in the majority of UFs. UF growth is largely dependent on steroid sex hormones, as the tumor is rather uncommon before menarche. The conversion of a normal myometrial stem cell into a tumor-initiating stem cell is the first link of complex UF biology. Steroid hormones induce the expression of genes, growth factors, and cytokines, which is the cause of UF cell division and ECM production. Some of the best elucidated pathways in UFs include Smad proteins, extracellular signal-regulated kinases, phosphoinositide 3-kinase, and wingless type/β-catenin. Moreover, early life exposure to endocrine disrupting chemicals has been shown to increase incidence of tumor formation in animal models with involvement of excessive inflammation and DNA repair impairment in exposed myometrium stem cells.

Numerous treatment modalities are available ranging from completely non-invasive treatments with the use of drugs or various new devices, through minimally invasive procedures including myomectomies, and ending with hysterectomy. Several different compounds may modulate growth factors and, subsequently, their signaling pathways, which results in tumor volume reduction and the alleviation of symptoms. Hormonal therapies have been widely used for the treatment of symptoms caused by UFs. However, many of them are ineffective and symptoms usually recur after the discontinuation of selected agents. Ongoing research constantly contributes to the development of knowledge concerning non-hormonal substances influencing the biology of UFs and their potential use in therapy. Interestingly, natural compounds and small molecules are exciting non-hormonal therapies to be considered for uterine fibroids.

Therefore, we see the area for new studies regarding known but not yet fully elucidated pathways as well as novel treatment options and approaches. It is vital that this Special Issue includes the presentation of new biological pathways involved in the development and growth of UFs and substances by which they are influenced. We also want to present new compounds which present anti-UF activity or combined therapies which aim at the reduction of invasiveness with a simultaneous increase in the effectiveness of UF treatment.

Prof. Dr. Ayman Al-Hendy
Prof. Dr. Michał Ciebiera
Dr. Mohamed Ali
Guest Editors

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• Uterine fibroid
• Leiomyoma
• Development
• Fibrosis
• Extracellular matrix
• Risk factors
• Endocrinology
• Genetics
• Pathophysiology
• Pharmacology
• Hormonal therapy
• Non-hormonal therapy
• Synergisms
• Minimally invasive therapy
• Promising therapies
• Epigenetics
• Early life exposure
• Developmental reprogramming
• Ethnic disparity