Are Angiogenic Growth Factors the Future of Fibroid Therapy?

Angiogenic growth factors play an important role in the mechanisms of fibroid pathophysiology, including abnormal vasculature and fibroid growth and survival, according to the results of a literature review.

Angiogenesis is the physiological process through which new blood vessels form from existing vessels. However, it is also a fundamental step in the transition of tumors from a benign state to a malignant one. Although uterine fibroids are benign growths in most cases and tend to have reduced vascularization, angiogenesis may play a role in their growth and development.

“It is well established that tumors are dependent on angiogenesis for their growth and survival. Although uterine fibroids are known to be benign tumors with reduced vascularization, recent work demonstrates that the vasculature of fibroids is grossly and microscopically abnormal,” the review authors wrote. “Accumulating evidence suggests that angiogenic growth factor dysregulation may be implicated in these vascular and other features of fibroid pathophysiology.”

In a review of relevant studies, the authors found multiple growth factors that are involved in angiogenesis, including epidermal growth factor (EGF), heparin-binding EGF, vacular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, and adrenomedullin, are differentially expressed in leiomyoma (benign neoplasms that arise from smooth muscle) compared with normal myometrium.

“An important paradox is that although leiomyoma tissues are hypoxic, leiomyoma feature down-regulation of key molecular regulators of the hypoxia response. Furthermore, the hypoxic milieu of leiomyoma may contribute to fibroid development and growth,” the authors explained.

This is most notable in that common treatments of fibroids, such as GnRH agonists and uterine artery embolization, work at least in part via anti-angiogenic mechanisms.

This evidence suggests that angiogenic growth factors play an important role in mechanisms of fibroid pathophysiology, particularly abnormal vasculature and fibroid growth and survival.

“Moreover, the fibroid’s abnormal vasculature, together with its aberrant hypoxic and angiogenic response, may make it especially vulnerable to disruption of its vascular supply, a feature which could be exploited for treatment,” the authors wrote.

To better understand the role of growth factors in normal and pathological myometrial angiogenesis, additional studies are needed. However, the available evidence suggests that there may be some potential for anti-angiogenic strategies in the treatment of uterine fibroids.

Pertinent Points:
- Angiogenic growth factors play an important role in the the mechanisms of fibroid pathophysiology.
- There may be potential for anti-angiogenic treatment strategies for uterine fibroids.
- Experimental studies are needed to better understand how angiogenic growth factors are involved in normal and pathological myometrial angiogenesis.

References:

Tal R, Segars JH. The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy. Hum Reprod Update. 2013 Sep 29. [Epub ahead of print]