05 Nov Beta Blocker Rapidly Shrank Vascular Malignant Angiosarcoma
MedicalResearch.com Interview with:
Dr. Brad A. Bryan Ph.D Assistant Professor
Texas A&M University Health Science Center, Houston, TX
Department of Biomedical Sciences
Texas Tech University Health Sciences Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Bryan: In 2008 it was serendipitously discovered that the beta blocker propranolol was effective in treating a common benign pediatric vascular tumor called infantile hemangioma. Over the past few years, my lab has been working on elucidating the molecular mechanisms underlying this pediatric tumor and part of this research involved uncovering how propranolol selectively inhibited these tumors. At the same time these studies were taking place, other members of my lab were working on pre-clinical drug development for a malignant vascular tumor called angiosarcoma. Patients with angiosarcoma are faced with very few effective treatment options and abysmal survival rates, so we decided to see if the efficacy of beta blockade observed in infantile hemangiomas transferred to angiosarcomas. Using preclinical in vitro and in vivo assays, we demonstrated that propranolol was very effective at inducing cell death, blocking migration, and inhibiting tumor growth in our angiosarcoma models. This work was subsequently published in Plos One (Stiles et al., 2013). I then collaborated with Dr. William Chow from San Francisco to test propranolol off-label (propranolol is FDA approved to treat high blood pressure, heart dysrhythmias, thyrotoxicosis, and essential tremors) in a patient suffering from a rapidly expanding angiosarcoma covering a large portion of his face. In the window between diagnosis of the tumor and the start of chemotherapy, we placed the patient on oral propranolol. The redness of the tumor very rapidly lessened and remarkably by only one week of treatment the tumor margins appeared to significantly shrink. We examined biospies of the tumor before and after only one week of propranolol and found that the proliferation of the tumor cells was markedly decreased following beta blockade. After a combination of propranolol, chemotherapy, and radiation that lasted several months, the patient had no detectable metabolically active tumor or distant metastases. We published these findings in JAMA Dermatology (Chow et al., 2015).
Medical Research: What should clinicians and patients take away from your report?
Dr. Bryan: Propranolol is very inexpensive, has minimal side effects, and shows promise for the treatment of malignant vascular tumors. Our study was limited to only one patient due to the rarity of angiosarcomas, however Banavali et al. recently published a similar report in Ecancermedicalscience (2015) indicating that a combination of propranolol and metronomic chemotherapy resulted in a sustained complete response in a patient with a relapsing metastatic angiosarcoma. Retrospective analysis performed by Anil Sood’s lab at MD Anderson show clinical efficacy of beta blockers in ovarian and breast cancer. There is a lot of preclinical and clinical evidence suggesting that beta blockade may be effective against not only infantile hemangiomas and angiosarcomas, but may extend to more common malignant tumors.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Bryan: Prospective clinical trials are needed to state whether propranolol truly shows efficacy against these tumors. We can publish case reports and retrospective studies over and over again, but in the end we need to compare cohorts of patients treated with propranolol to those that receive placebo. Dr. Zeina Nahleh (TTUHSC Department of Internal Medicine) and I are currently funded through a pilot grant to test the ability of propranolol to induce tumor apoptosis and decrease the tumor proliferative index in patients with breast cancer in the window between diagnosis and surgical removal. This is registered as a Phase II study and we are currently enrolling patients at the University Medical Center of El Paso. Our results will be released at the end of 2016 and after analyzing these results we can shed some better light on whether propranolol is effective against breast cancer or if there are stratified patient populations that could most benefit from use of this drug.
Chow W, Amaya CN, Rains S, Chow M, Dickerson EB, Bryan BA. Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated β-Blockade. JAMA Dermatol. Published online September 16, 2015. doi:10.1001/jamadermatol.2015.2554.
Dr. Brad A. Bryan Ph.D (2015). Beta Blocker Rapidly Shrank Vascular Malignancy Angiosarcoma
Last Updated on November 5, 2015 by Marie Benz MD FAAD