Preventing Melanoma Progression by Targeting Nonclassical Androgen Signaling
Abstract
Melanoma is associated with exposure to solar UV radiation, and disproportionally affects males. Military personnel often spend significant time outdoors, are 80% male across all branches, and are therefore at especially high melanoma risk. We have strong preliminary data showing that increased melanoma burden in males results from far more than just differences in environmental exposure to sunlight. In laboratory mice housed inside, melanomas grow much more aggressively in male mice than in female mice. Our findings suggest that the male hormone testosterone is responsible for much of this difference. Our pilot studies show that the testosterone effects in melanoma result from testosterone binding to a protein in melanoma cells called ZIP9, which was first discovered as a transport protein for zinc. There are no drugs that were designed to target ZIP9, however, we discovered that drugs approved for prostate cancer do inhibitZIP9 in melanoma, and inhibit the growth of melanomas in male mice. Because apalutamide is routinely used in people, and is well tolerated, this proposal has the potential to rapidly translate to new melanoma trials.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1203910
Entities
People
- Todd Ridky
Organizations
- University of Pennsylvania