In cell culture and mice studies, bazedoxifene inhibited estrogen-induced gene expression and cell proliferation in cancer cells, including those that were tamoxifen-resistant.
Studies show a selective estrogen modulator receptor (SERM) drug approved in Europe for the treatment and prevention of osteoporosis in postmenopausal women may also inhibit the growth of breast cancer cells.
According to a news release from Duke Medicine News and Communications, researchers from Duke University School of Medicine presented study results at ENDO 2013: The Endocrine Society’s 95th Annual Meeting & Expo that indicated the drug bazedoxifene “packs a powerful one-two punch that not only prevents estrogen from fueling breast cancer cell growth, but also flags the estrogen receptor for destruction.”
The researchers tested bazedoxifene in mice and in multiple models of human-derived breast cancer cell lines, including cells that had developed resistance to tamoxifen, aromatase inhibitors, and lapatinib, a “targeted therapy that is used to treat patients with advanced breast cancer whose tumors contain the mutant HER2 gene.”
Lead author Suzanne Wardell, PhD, said because SERM drugs like bazedoxifene remove the estrogen receptor “as a target by degradation, it is less likely the cancer cell can develop a resistance mechanism because you are removing the target.” This research showed that “the estrogen receptor is still a good target, even after its resistance to tamoxifen has developed.”
In their abstract of the study results, the authors wrote that their research showed bazedoxifene “effectively inhibited the growth of both tamoxifen-sensitive and tamoxifen-resistant breast tumor xenografts.” Further, bazedoxifene induced “a unique conformational change” in estrogen receptor (ERα) structure that “results in its proteasome dependent degradation in cellular and xenograft models of breast cancer.” Based on these results, the researchers “determined that competitive antagonism by [bazedoxifene] was sufficient to block ERα transactivation and breast cancer cell proliferation.”
Based on these results, the authors of the study concluded that bazedoxifene “or other SERMs that exhibit the pharmacological properties of a pure antagonist, may be effective in the treatment and prevention of breast cancer. Bazedoxifene has recently been approved for use in the European Medicines Agency for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer.”