JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
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CitationYeh, Jennifer E, Patricia A Toniolo, and David A Frank. 2013. “JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition.” JAK-STAT 2 (4): e24635. doi:10.4161/jkst.24635. http://dx.doi.org/10.4161/jkst.24635.
AbstractA recent article published by Britschgi et al. in Cancer Cell, “JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer,” describes a positive feedback loop of JAK2/STAT5 activation that drives resistance to PI3K/mTOR inhibition in breast cancer. The authors found that genetic or pharmacological inhibition of JAK2 circumvents resistance to PI3K/mTOR inhibition and go on to show the efficacy of combined PI3K/mTOR and JAK2 inhibition on reducing cancer cell number, tumor growth, and metastasis as well as increasing in vivo survival. These results provide strong support for combination therapy with JAK2/STAT5 and PI3K/mTOR inhibitors in breast cancer. Here we discuss how the article by Britschgi et al. proposes a novel mechanism to explain how breast cancer cells overcome inhibition of a key signaling pathway driving cell proliferation. We also discuss the interplay between activation of the transcription factors STAT5 and STAT3 in breast cancer.
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