- Sir Peter MacCallum Department of Oncology - Research Publications
Sir Peter MacCallum Department of Oncology - Research Publications
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ItemA2A blockade enhances anti-metastatic immune responsesBeavis, PA ; Milenkovski, N ; Stagg, J ; Smyth, MJ ; Darcy, PK (TAYLOR & FRANCIS INC, 2013-12)The specific targeting of tumor-elicited immunosuppression is a promising strategy for the treatment of cancer. We have recently demonstrated that targeting the immunosuppressive pathway mediated by CD73-derived adenosine through the blockade of A2A/A2B adenosine receptors significantly reduced the metastatic potential of CD73+ breast carcinomas and melanomas via both immunological and non-immunological mechanisms.
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ItemNo Preview AvailableCD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancerLoi, S ; Pommey, S ; Haibe-Kains, B ; Beavis, PA ; Darcy, PK ; Smyth, MJ ; Stagg, J (NATL ACAD SCIENCES, 2013-07-02)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.