Tamoxifen inhibits keloid formation
February 1, 1998 2 minutes read
Tamoxifen inhibits keloid formation
Cancer drug carries added benefit
Tamoxifen, the chemotherapeutic agent given to women with breast cancer, may be effective for preventing proliferative scar disorder, in which keloids grow outside the boundaries of the original wound. The condition affects an estimated 30 million to 40 million Americans, according the American College of Surgeons.Current treatments for the condition include surgical excision, radiotherapy, cryotherapy, lasers, electricity, pressure therapy, and steroids. Treatment efficacy is limited, and the keloids tend to return.
John S. Mancoll, MD, assistant professor of surgery in the Division of Plastic Surgery at the University of Texas in Galveston, began studying tamoxifen because of its potential to cause wound-healing problems for women who take the drug for breast cancer. "We know that some anti-tumor drugs may inhibit wound healing. The concern arose that women treated with tamoxifen may be a new group of patients who have problems with wound healing," he says.
After animal studies confirmed that tamoxifen inhibited wound healing, Mancoll wondered how this negative effect could be turned into a positive one. "We said, What scenarios do we have where there is too much wound healing?’ And keloids was at the top of the list," he explains.
Mancoll and colleague Michael T. Longaker at New York University explored one of the ways that tamoxifen stops the growth of keloid scars. They discovered that the drug inhibits fibroblast formation by acting on transforming growth factor-beta (TGF-beta). In a study presented at the 1997 Clinical Congress of the American College of Surgeons, Mancoll and his colleagues demonstrated for the first time that tamoxifen has a dose-dependent effect on TGF-Beta.
A dose of 8 mcg/mL of tamoxifen cut keloid fibroblast production by 85%; a dose of 4 mcg/mL produced a 49% reduction in keloid fibroblast growth.
"The exciting thing about these results was that we found a dose range that enables you to use tamoxifen to treat a wound, but also provides a way to turn the effect of tamoxifen off. So we may have control over how we can use the drug," says Mancoll.
Mancoll is currently developing a topical formation of tamoxifen that may be tried in patients with keloids. One problem, he explains, will be developing a topical formation that will penetrate the skin. He hopes such a topical formation will be ready to enter clinical trials some time this year.
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