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CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer.


ABSTRACT: Using gene-expression data from over 6,000 breast cancer patients, we report herein that high CD73 expression is associated with a poor prognosis in triple-negative breast cancers (TNBC). Because anthracycline-based chemotherapy regimens are standard treatment for TNBC, we investigated the relationship between CD73 and anthracycline efficacy. In TNBC patients treated with anthracycline-only preoperative chemotherapy, high CD73 gene expression was significantly associated with a lower rate of pathological complete response or the disappearance of invasive tumor at surgery. Using mouse models of breast cancer, we demonstrated that CD73 overexpression in tumor cells conferred chemoresistance to doxorubicin, a commonly used anthracycline, by suppressing adaptive antitumor immune responses via activation of A2A adenosine receptors. Targeted blockade of CD73 enhanced doxorubicin-mediated antitumor immune responses and significantly prolonged the survival of mice with established metastatic breast cancer. Taken together, our data suggest that CD73 constitutes a therapeutic target in TNBC.

SUBMITTER: Loi S 

PROVIDER: S-EPMC3704029 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer.

Loi Sherene S   Pommey Sandra S   Haibe-Kains Benjamin B   Beavis Paul A PA   Darcy Phillip K PK   Smyth Mark J MJ   Stagg John J  

Proceedings of the National Academy of Sciences of the United States of America 20130617 27


Using gene-expression data from over 6,000 breast cancer patients, we report herein that high CD73 expression is associated with a poor prognosis in triple-negative breast cancers (TNBC). Because anthracycline-based chemotherapy regimens are standard treatment for TNBC, we investigated the relationship between CD73 and anthracycline efficacy. In TNBC patients treated with anthracycline-only preoperative chemotherapy, high CD73 gene expression was significantly associated with a lower rate of pat  ...[more]

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