Epigenetic synthetic lethality in ovarian clear cell carcinoma: EZH2 and ARID1A mutations Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Saturday, June 18, 2016

Epigenetic synthetic lethality in ovarian clear cell carcinoma: EZH2 and ARID1A mutations



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 In addition to ARID1A mutation, the phosphoinositide 3-kinase (PI3K)/protein kinase B (best known as AKT), pathway is often activated in OCCC as a result of gain-of-function mutations in PIK3CA, the gene encoding the catalytic subunit of PI3K. Indeed, conditional Arid1a knockout together with activation of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit α isoform (Pik3ca) leads to the development of OCCC in genetic mouse models.10 Interestingly, the validated ARID1A/EZH2 target gene PIK3IP1 is a negative regulator of PI3K. These findings suggest that ARID1A mutation cooperates with PI3K/AKT signaling to drive OCCC. Thus, a combination of the EZH2 inhibitor together with inhibition of the PI3K/AKT pathway may carry an even greater clinical benefit.
 http://www.tandfonline.com/na101/home/literatum/publisher/tandf/journals/content/kmco20/2016/kmco20.v003.i01/23723556.2015.1032476/20160216/images/medium/kmco_a_1032476_f0001_oc.gif

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