Non-selective beta blockers inhibit angiosarcoma cell viability and increase progression free- and overall-survival in patients diagnosed with metastatic angiosarcoma
Clarissa N. Amaya 1, Mariah Perkins 2, Andres Belmont 3, Connie Herrera 3, Arezo Nasrazadani 3, Alejandro Vargas 3 Thuraieh Khayou 1, Alexa Montoya 1,4, Yessenia Ballou 1, Dana Galvan 3, Alexandria Rivas 1, Steven Rains 1, Luv Patel 3, Vanessa Ortega 1, William Chow 5 Erin B. Dickerson 6,7 and Brad A. Bryan 1,3
1 Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA
2 Department of Biochemistry, Baylor University, Waco, TX, USA
3 Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
4 Department of Biology, University of Texas, El Paso, TX, USA
5 Mohs Micrographic Surgery and Cutaneous Oncology, San Leandro, CA, USA
6 Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN, USA
7 Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
Correspondence to:
Brad A. Bryan, email: [email protected]
Keywords: angiosarcoma, propranolol, beta blocker, sarcoma
Received: January 09, 2018 Accepted: March 02, 2018 Published: April 29, 2018
Abstract
Patients with metastatic angiosarcoma undergoing chemotherapy, radiation, and/or surgery experience a median progression free survival of less than 6 months and a median overall survival of less than 12 months. Given the aggressive nature of this cancer, angiosarcoma clinical responses to chemotherapy or targeted therapeutics are generally very poor. Inhibition of beta adrenergic receptor (β-AR) signaling has recently been shown to decrease angiosarcoma tumor cell viability, abrogate tumor growth in mouse models, and decrease proliferation rates in preclinical and clinical settings. In the current study we used cell and animal tumor models to show that β-AR antagonism abrogates mitogenic signaling and reduces angiosarcoma tumor cell viability, and these molecular alterations translated into patient tumors. We demonstrated that non-selective β-AR antagonists are superior to selective β-AR antagonists at inhibiting angiosarcoma cell viability. A prospective analysis of nonselective β-AR antagonists in a single arm clinical study of metastatic angiosarcoma patients revealed that incorporation of either propranolol or carvedilol into patients’ treatment regimens leads to a median progression free and overall survival of 9 and 36 months, respectively. These data suggest that incorporation of non-selective β-AR antagonists into existing therapies against metastatic angiosarcoma can enhance clinical outcomes.
PII: 413
