Enhancing Targeted α-therapy for treatment of metastatic breast cancer

Metastatic cancer remains the major cause of mortality in cancer patients, including breast cancer patients. Breast cancer patients with metastatic disease have a significantly lower five-year survival rate (26%) compared to a patient with localized cancer (99%). Breast cancer patients that have an overexpression of human growth factor receptor-2 (HER2) are associated with a poorer prognosis including a higher potential to metastasize and a higher likelihood to have disease reccurrence. Previously, in a lung metastasis mouse model of breast cancer our lab demonstrated that an anti-HER2 antibody labeled with 225Ac, 225Ac-DOTA-anti-7.16.4, was able to eradicate metastatic disease in 67% of mice while mice having disseminated disease showed only a significant increase in survival. The aim of this study is to investigate biological response modifiers (BRMs) that will reduce the proliferation rate of HER2 (17-AAG), decrease double stranded break repair (Nu7441), or increase the permeability of targeted tumors (TNF-α) to potentially augment targeted alpha therapy.

NEDROW Jessie;  MCCARTY Greg;  JOSEFSSON Anders;  RAY Sangeeta;  CORTEZ Angel;  SONG Hong;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  SGOUROS G.; 

2018-11-12

SPRINGER

JRC111783

1619-7070 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC111783,   

10.1007/s00259-018-4148-3 (online),