A Systematic Review of the Role of Senescent Cells in Uterine Leiomyomas: Deciphering Molecular Pathways and Exploring Therapeutic Prospects

Authors

• Shelby Howard, LSU Health Sciences Center - New OrleansFollow
• Akanksha Suresh, Johns Hopkins University, Baltimore, MD
• Morgan Bou Zerdan, American University of Beirut, Beirut, Lebanon
• Md Soriful Islam, Johns Hopkins University School of Medicine, Baltimore, MD
• Samya El Sayed, Johns Hopkins University, Baltimore, MD
• Rachel Michel, Johns Hopkins University, Baltimore, MD
• Mostafa Borahay, Johns Hopkins University, Baltimore, MD
• Sushma Nagaraj, Johns Hopkins University, Baltimore, MD
• Jennifer Elisseeff, Johns Hopkins University, Baltimore, MD
• Jude Phillips, Johns Hopkins University, Baltimore, MD
• Emily Joseph, Johns Hopkins University, Baltimore, MD
• Bhuchitra Singh, Johns Hopkins University, Baltimore, MD
• James H. Segars, Johns Hopkins University, Baltimore, MD

Document Type

Article

Publication Date

5-5-2026

Publication Title

Reproductive Sciences

Abstract

Uterine leiomyomas (ULs) are prevalent benign tumors in women of reproductive age characterized by cellular senescence. Cellular senescence is a state of stable, irreversible cell cycle arrest characterized by discrete changes in cellular morphology and gene expression. This systematic review, following PRIMSA guidelines, evaluated the molecular pathways contributing to senescence in ULs and the use of novel therapeutic agents to target senescence. Two investigators independently screened and identified relevant articles written in English involving human subjects. Sixty-nine articles were identified; 11 studies met criteria. Multiple studies recognized a range of biomarkers of senescence in ULs including senescence associated beta galactosidase (SA-β-gal), senescent associated proteins (p16, p21, p14ARF), and telomere shortening. Key pathways such as AKT and p14ARF-TP53-p21, and genes such as HMGA2 and MED12 have been implicated in regulating the balance between tumor proliferation and growth arrest and senescence. However, the specific genetic and epigenetic mechanisms that induce and maintain senescence in ULs are not fully understood. There is growing interest in investigating whether senescent cells can be therapeutically targeted in ULs by senolytic agents that induce apoptosis, and senomorphic agents that modulate the senescence-associated secretory phenotype (SASP) to reduce its pro-tumorigenic effects. While limited, non-clinical data suggests this approach may be promising, further investigation is needed to establish their clinical efficacy in patients with ULs.

First Page

853

Last Page

863

PubMed ID

42086971

Volume

33

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Howard, Shelby; Suresh, Akanksha; Zerdan, Morgan Bou; Islam, Md Soriful; Sayed, Samya El; Michel, Rachel; Borahay, Mostafa; Nagaraj, Sushma; Elisseeff, Jennifer; Phillips, Jude; Joseph, Emily; Singh, Bhuchitra; and Segars, James H., "A Systematic Review of the Role of Senescent Cells in Uterine Leiomyomas: Deciphering Molecular Pathways and Exploring Therapeutic Prospects" (2026). School of Medicine Faculty Publications. 4720.
https://digitalscholar.lsuhsc.edu/som_facpubs/4720
10.1007/s43032-026-02075-x