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Breast cancer

Phosphoinositide 3-kinase (PI3K); mammalian target of rapamycin (mTOR; FRAP; RAFT1); Janus kinase-2 (JAK-2)

In vitro and mouse studies suggest JAK-2 inhibitors could help increase the efficacy of PI3K and mTOR inhibitors against triple-negative breast cancer. In cancer cell lines, a dual PI3K and mTOR inhibitor increased JAK-2 expression compared with vehicle. In a mouse xenograft model of human breast cancer, a PI3K and mTOR inhibitor plus a JAK-2 inhibitor synergistically decreased tumor growth and metastasis and increased overall survival compared with either compound alone. Next steps could include testing the combination in additional animal models.
At least 28 companies have PI3K or mTOR inhibitors in development stages ranging from preclinical to marketed to treat cancers.
At least 10 companies have JAK-2 inhibitors in clinical and preclinical testing for various indications.

SciBX 6(2); doi:10.1038/scibx.2013.32
Published online Jan. 17, 2013

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Britschgi, A. et al. Cancer Res.; published online Dec. 11, 2012;
Contact: Mohamed Bentires-Alj, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland