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Propranolol repurposed to treat soft tissue sarcomas

Propranolol, a drug used to treat high blood pressure, is being repurposed for soft tissue sarcoma treatment in Europe. The European Commission recently granted propranolol Orphan Drug Designation, a status assigned to a medicine intended for use against a rare condition. The medicine must fulfill certain criteria for designation as an orphan medicine so that it can benefit from incentives such as protection from competition once on the market.

Propranolol is a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins). Propranolol is used to treat tremors, angina (chest pain), hypertension (high blood pressure), heart rhythm disorders, and other heart or circulatory conditions. It also is used to treat or prevent heart attack, and to reduce the severity and frequency of migraine headaches.

“People with soft tissue sarcomas have a very poor survival rate,” said Brad Bryan, Ph.D., a biomedical scientist at Texas Tech University Health Sciences Center El Paso. “Four out of 10 patients with the cancer will die and are in urgent need of new treatment options.”

According to a news release by TTUHCS, propranolol's ability to treat angiosarcoma — a lethal form of soft tissue sarcoma — originally was discovered by Bryan's TTUHSC El Paso lab. In his study, Bryan used cell lines and animal models to show that propranolol could fight angiosarcoma and remarkably reduce the growth of tumors; the results were published in a 2013 PLOS One paper. [1]

Angiosarcoma is a cancer of the inner lining of blood vessels, and it can occur in any area of the body. The disease most commonly occurs in the skin, breast, liver, spleen, and deep tissue.

In a 2015 JAMA Dermatology article, Bryan described treating a patient with angiosarcoma — who only had months left to live — and bringing the tumor down to undetectable levels. What's more, the treatment had little to no side effects. [2]

Several scientists across the world have reported similar results since then, testing propranolol on their own patients with angiosarcoma.

“What surprised us the most about this new treatment is the fact that we got 100 percent clinical response, which is defined as either tumor regression or stabilization of the disease,” said Eddy Pasquier, Ph.D., a researcher at the University of Aix-Marseille. “This is not a cure in the sense that most patients will eventually see their disease progress, but this level of response is still very impressive, especially in this patient population with a very bleak prognosis; we're talking patients whose prognosis was roughly one year, give or take a few months.”

Propranolol also is relatively cost efficient. Developed in the 1960s, today propranolol is a generic drug and costs about $4 a month. Compare that to current prescription drug therapies for sarcomas that can cost about $10,000 a month.

“Treating soft tissue sarcoma can easily top $100,000 to $200,000,” Bryan said. “While propranolol will certainly not replace these treatments, our data show it improves the ability of the treatments to work — all at the cost of a generic co-pay.”

References

  1. Stiles, J., Amaya, C., Rains, S., Diaz, D., Pham, R., & Battiste, J. et al. (2013). Targeting of Beta Adrenergic Receptors Results in Therapeutic Efficacy against Models of Hemangioendothelioma and Angiosarcoma. Plos ONE, 8(3), e60021. doi:10.1371/journal.pone.0060021
  2. Chow, W., Amaya, C., Rains, S., Chow, M., Dickerson, E., & Bryan, B. (2015). Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated β-Blockade. JAMA Dermatology, 151(11), 1226. doi:10.1001/jamadermatol.2015.2554;

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