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Breast cancer

Homeobox C10 (HOXC10)

In vitro and mouse studies suggest decreasing HOXC10 methylation could help treat breast cancers resistant to aromatase inhibitors and other estrogen-depleting therapies. In human breast cancer cell lines, silencing HOXC10 via histone and DNA hypermethylation was associated with resistance to estrogen deprivation. In an estrogen-deprived mouse xenograft model of breast cancer, silencing HOXC10 expression increased tumor growth compared with unmodified HOXC10 expression. In patients with breast cancer who received aromatase inhibitor therapy, recurrent tumors had lower HOXC10 protein levels than primary tumors. Future studies could include testing aromatase inhibitors and DNA hypomethylating agents in mouse models of breast cancer.
Celgene Corp., Pfizer Inc. and Nippon Shinyaku Co. Ltd. market Vidaza azacitidine, a hypomethylating agent that inhibits DNA methyltransferase, to treat myelodysplastic syndrome (MDS). Celgene and Pfizer market Vidaza to treat acute myelogenous leukemia (AML).
Otsuka Pharmaceutical Co. Ltd., Eisai Co. Ltd. and Johnson & Johnson market Dacogen decitabine, a hypomethylating agent that inhibits DNA methyltransferase, to treat MDS and AML.
Celgene has CC-486, an oral formulation of azacitidine, in
Phase II trials to treat MDS and Phase I testing to treat solid tumors.

SciBX 7(16); doi:10.1038/scibx.2014.451
Published online April 24, 2014

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Pathiraja, T.N. et al. Sci. Transl. Med.; published online March 26, 2014;
Contact: Steffi Oesterreich, Women's Cancer Research Center at the University of Pittsburgh, Pittsburgh, Pa.