Everolimus Found to Improve Chemotherapy-Induced Infertility in Preclinical Research
When ovarian follicles become a target of cyclophosphamide, a woman's fertility may be affected.
Everolimus, a drug presently used to slow tumor growth, may also combat infertility caused by standard chemotherapies. In a study published in the Proceedings of the National Academy of Sciences, researchers found that mice treated with a combination cyclophosphamide and everolimus or INK128, which slow tumor growth, had twice as many offspring as mice that were treated with cyclophosphamide alone. 1
Cyclophosphamide damages the DNA of rapidly multiplying tumor cells, but also stimulates mTOR expression in the ovaries. mTOR is implicated in increased cell growth, which causes ovarian follicles to quickly multiply. Thus, ovarian follicles become a target of cyclophosphamide, impairing a woman's fertility.
The researchers tested the effect of 2 drugs known to inhibit the mTOR pathway and slow tumor growth. Using mouse cells, which undergo the same process of maturation as human cells, the researchers exposed the mice to either cyclophosphamide alone or in combination with an mTOR inhibitor (everolimus or INK128). Mice who received the cyclophosphamide/mTOR inhibitor combination had an average of 7.4 pups, whereas mice who received just cyclophosphamide had an average of 3.4 pups. Additionally, mice who received just cyclophosphamide had a 64% reduction in the number of primordial follicles compared with the control mice.
In addition to mTOR inhibitors being a solution to infertility caused by chemotherapy, the researchers are also exploring the possibility that mTOR inhibitors may be effective in women suffering from general infertility.
Reference1. Goldman KN, Chenette D, Arju R, et al. mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy. Proc Natl Acad Sci U S A. 2017 Mar 7. doi: 10.1073/pnas.1617233114 [Epub ahead of print]