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Breast cancer

Transforming growth factor-b (TGFB; TGFb); TGFb receptor II (TGFb-RII; TGFBR2)

Mouse studies suggest inhibiting TGFb signaling could help improve chemotherapy efficacy in breast cancer. In two orthotopic mammary carcinoma mouse models, inhibition of TGFb signaling with a TGFb-neutralizing mAb or overexpression of soluble TGFBR2 decreased tumor growth and metastasis compared with no inhibition or normal TGFBR2 expression. In these mouse models, compared with wild-type mice, the TGFb-neutralizing mAb and soluble TGFBR2 overexpression both increased the intratumoral distribution and effects of Doxil doxorubicin. Next steps could include testing TGFb-neutralizing mAbs in combination with chemotherapy in additional types of cancer.
Johnson & Johnson markets Doxil liposomal doxorubicin to treat various cancers.
At least four companies have compounds that inhibit TGFb signaling in Phase II testing or earlier to treat various cancers.

SciBX 5(39); doi:10.1038/scibx.2012.1025
Published online Oct. 4, 2012

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Liu, J. et al. Proc. Natl. Acad. Sci. USA; published online Sept. 20, 2012;
Contact: Lei Xu, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
Contact: Rakesh K. Jain, same affiliation as above