Study finds it may be possible to treat endometriosis using an investigational cancer drug

Researchers at the University of Edinburgh have shown that the painful symptoms of endometriosis could potentially be alleviated using a drug that has so far been investigated as a treatment for cancer.

endometriosisImage Credit: Iryna Inshyna / Shutterstock.com

They found that treating endometrial cells with the drug reduced production of the potentially harmful waste product lactate and prevented aberrant cell growth.

Endometriosis is a common and chronic condition

Endometriosis is a chronic, painful condition that affects approximately 176 million women globally. It is characterized by the growth of endometrium-like tissue (lesions) outside of the womb, usually on the pelvic peritoneum.

Currently, there is no cure for endometriosis, and treatment is difficult. All drugs that have been approved are contraceptives, which limits their use among women of child-bearing age. The drugs are also associated with unpleasant side effects. Lesions can be surgically removed, but recurrence rates post-surgery are as high as 50% after five years.

What has the University of Edinburgh team found?

The University of Edinburgh researchers found that human peritoneal mesothelial cells (HPMCs) taken from the pelvic peritoneum of women with endometriosis exhibit a different metabolism, compared with women who do not have the disease.

The authors say the cells "exhibit significantly higher glycolysis, lower mitochondrial respiration, decreased enzymatic activity of pyruvate dehydrogenase (PDH), and increased production of lactate compared to HPMCs from women without disease."

This resembles the behavior of cancer cells, which are programmed to use aerobic glycolysis to increased lactate secretion.

"In tumors, lactate is considered a key factor in driving cell invasion, angiogenesis, and immune suppression, changes that are also implicated in the establishment and survival of endometriosis lesions," writes Andrew Horne and team.

Using an investigational cancer drug as a treatment

As reported in the Proceedings of the National Academy of Sciences, the researchers treated HPMCs from women who had endometriosis with a PDH activator that has previously been investigated as a cancer drug.

As a result, HPMC metabolism normalized, and lactate production reduced. The treatment also abrogated the proliferation of endometrial cells co-cultured with pelvic cells.

Furthermore, oral administration of the drug in a mouse model of endometriosis significantly reduced lactate levels and the size of endometrial lesions.

A potential non-contraceptive option for women

The team thinks their findings could lead to new treatments for women who cannot or do not want to take contraceptives or to prevent recurrence post-surgery.

"These findings provide the rationale for targeting metabolic processes as a non-contraceptive treatment for women with endometriosis either as a primary nonhormonal treatment or to prevent recurrence after surgery," writes the team.

Horne and colleagues are now conducting an early-phase clinical trial to confirm the study findings

Wellbeing of Women and the Medical Research Council funded the research

The research was funded by the charity Wellbeing of Women and the Medical Research Council (MRC) UK.

Wellbeing of Women supports efforts to find cures and treatments across a range of female reproductive health problems with the aim of transforming women's lives and giving babies the best start in life.

CEO of Wellbeing of Women, Janet Lindsay, says: "More than 176 million women suffer from endometriosis yet few people have heard of it and treatment, which can impact fertility, has progressed very little for over 40 years.

"This is why we are so excited by the findings of this research that Wellbeing of Women has funded and which could lay the basis for the first new non-hormonal treatment offering women a life-changing option. We are delighted that Professor Andrew Horne's new treatment going to clinical trial could hugely impact so many women's lives."

Horne, who works at the university's MRC Centre for Reproductive Health, also says endometriosis can be a life-changing condition for so many women.

Now that we understand better the metabolism of the cells in women that have endometriosis, we can work to develop a non-hormonal treatment,"

Professor Andrew Horne, MRC Centre for Reproductive Health, University of Edinburgh

Journal reference:

Horne et al. (2019). Repurposing dichloroacetate for the treatment of women with endometriosis. PNAS. DOI: https://doi.org/10.1073/pnas.1916144116

Sally Robertson

Written by

Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.

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