CD73: a new target for triple
negative breast cancer
, Sandra Pommey
, Benjamin Haibe
, Paul A. Beavis
, Phillip K. Darcy
Mark J. Smyth
Breast Cancer Translational Research Laboratory (BCTL) J.C.
Heuson, Institut Jules Bordet,
Boulevard de Waterloo, 125, 1000 Brussels, Belgium.
Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Faculté de Pharmacie
et Institut du Cancer de Montréal, Montréal, Québec, Canada, H2L 4M1.
Bioinformatics and Computational Genomics Laboratory, Institut de recherches cliniques de
Montréal, Montréal, Canada
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St.
Andrews Place, East Melbourne, Victoria 3002, Au
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010,
Triple negative breast cancer (TNBC),
defined by the absence of estrogen receptor (ER),
progesterone receptor (PR) and HER2 expression, accounts
20% of all breast cancers
characterized by a worse prognosis
compared to other
of breast cancer
here are currently no known molecular targets for this subgroup of breast cancer patients
gene expression data from over 6,000 breast cancer patients, we
that high CD73
expression is associated with a poor prognosis in
and positively correlated with
regimens are standard
treatment for TNBC, we investigated the relationship between CD73 and anthracycline efficacy.
n TNBC patients treated with doxorubicin (DOX)
only neoadjuvant chemotherapy, high
CD73 gene expression was significantly assoc
iated with a lower rate of pathological complete
response at surgery. Using mouse models of
, we demonstrated that
in tumor cells
chemoresistance to anthracycline by suppressing adaptive anti
immune responses via activ
ation of A2A adenosine receptors. Combining DOX with targeted
blockade of CD73
induced potent anti
tumor immune responses against TNBC and significantly
prolonged the survival of mice with established metastatic disease. Taken together, our data
at CD73 constitutes a new therapeutic target in TNBC.
We acknowledge funding
support from the Susan G. Komen for the Cure, the National Health and Medical Research
Council (NH&MRC) of Australia (1013667, 1007902), the Victorian Cancer Agency (EOI09_71),
e Canadian Institutes of Health Research and the Cancer Research Society of Canada.
: John Stagg