Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids.

Background: Uterine fibroids are highly prevalent, collagen-rich, mechanically stiff, fibrotic tumors for which new therapeutic options are needed. Increased extracellular matrix (ECM) stiffness activates mechanical signaling and Hippo/YAP promoting fibroid growth, but no prior studies have tested either as a therapeutic target. We tested the hypothesis that injection of a purified form of collagenase Clostridium histolyticum (CCH) that selectively digests type I and type III collagens would alter ECM stiffness, Hippo signaling, and selectively reduce fibroid cell growth.

Summary of the Proceedings of the Basic Science of Uterine Fibroids Meeting: New Developments February 28, 2020.

Scientists from multiple basic disciplines and an international group of physician-scientists from the field of obstetrics and gynecology presented recent studies and discussed new and evolving theories of uterine fibroid etiology, growth and development at The Basic Science of the Uterine Fibroids meeting, sponsored by the Campion Fund and the National Institute of Environmental Health Sciences. The purpose was to share up-to date knowledge and to stimulate new concepts regarding the basic molecular biology and pathophysiology of uterine fibroids, and to promote future collaborations. The meeting was held at the National Institute of Environmental Health Sciences in North Carolina on February 28, 2020.

A Phase I Clinical Trial to Assess Safety and Tolerability of Injectable Collagenase in Women with Symptomatic Uterine Fibroids.

Uterine fibroids feature excessive deposition of types I and III collagen. Previous ex vivo studies showed an FDA-approved collagenase (EN3835)-digested types I and III collagen fibers in fibroid tissues; however, collagenase had not been evaluated in vivo for effects on uterine fibroids. The objective was to assess the safety and tolerability of collagenase injection directly into uterine fibroids.

Evidence of biomechanical and collagen heterogeneity in uterine fibroids.

Objective: Uterine fibroids (leiomyomas) are common benign tumors of the myometrium but their molecular pathobiology remains elusive. These stiff and often large tumors contain abundant extracellular matrix (ECM), including large amounts of collagen, and can lead to significant morbidities. After observing structural multiformities of uterine fibroids, we aimed to explore this heterogeneity by focusing on collagen and tissue stiffness.