Estrogen-Negative Cancers Respond to Anti-Estrogenic Therapies
Published:13 Sep.2023 Source:Hokkaido University
A team of researchers from the Institute for Genetic Medicine (IGM) at Hokkaido University has uncovered how estrogen affects the tumor microenvironment and promotes tumor growth in ERα-negative cancers.
In TNBC, estrogen suppresses the induction of cytotoxic T cells, which typically recognize and destroy cancer cells. The researchers confirmed this observation in mice TNBC and colon cancer models, which do not have estrogen sensitivity; they then went one step further and studied the effects of anti-estrogenic therapy on these cancers in mice models. Therapy with fulvestrant, the most effective estrogen signal blocker currently approved for clinical use, suppressed the growth of tumor cells. Tumor growth was also suppressed by two other approved anti-estrogenic drugs, tamoxifen and anastrozole, confirming that estrogen signal-blocking was responsible.
Estrogen signal blockers modulate immune response to increase production of cytotoxic T cells, specifically by preventing the activity of estrogen. The team also showed that therapy combining estrogen signal blockers with a class of drugs called immune checkpoint inhibitors (ICIs) drastically suppresses tumor progression in mice models. Most notably, the combination of fulvestrant (anti-estrogenic) and anti-CTLA-4 (ICI) resulted in the complete suppression of TNBC tumor progression.