New research shows that testosterone promotes melanoma proliferation by activating a newly recognized nonclassical testosterone receptor in melanoma cells called ZIP9, a zinc transporter that is not intentionally targeted by any available therapeutics but is widely expressed in human melanoma. The study from researchers at the Perelman School of Medicine uses melanoma in animal models to show that drugs that target androgen receptors (AR) in prostate cancer can be effectively repurposed to block ZIP9 and thereby inhibit melanoma in men. The findings are published in the journal Cancer Research.
Melanoma and most other cancers occur more frequently, and have worse outcomes, in men compared to women. The American Cancer Society estimates about 106,110 new melanomas will be diagnosed (about 62,260 in men and 43,850 in women) in the United States in 2021, and about 7,180 people are expected to die from the disease (about 4,600 men and 2,580 women). While this sex difference has been recognized for decades, the reasons for the difference have largely remained elusive. While sex steroids are thought to be involved, the classical androgen and estrogen receptors generally considered necessary for sex steroid effects are not detectable in most melanomas.
“The male sex hormone testosterone increases the rate of melanoma cell proliferation because it acts through ZIP9 rather than through the classical testosterone receptors that are well studied in prostate cancer,” says senior author Todd Ridky, an associate professor of dermatology.
This study is the first to show that ZIP9 is a determinant of the male vs. female disparity in cancer, and establishes a novel mechanistic link between male androgens and melanoma pathobiology.
This story is by Caren Begun. Read more at Penn Medicine News.