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Dasatinib/ARID1A Synthetic Lethality in OCCC
New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to ...
Source: Molecular Cancer Therapeutics - July 4, 2016 Category: Cancer & Oncology Authors: Miller, R. E., Brough, R., Bajrami, I., Williamson, C. T., McDade, S., Campbell, J., Kigozi, A., Rafiq, R., Pemberton, H., Natrajan, R., Joel, J., Astley, H., Mahoney, C., Moore, J. D., Torrance, C., Gordan, J. D., Webber, J. T., Levin, R. S., Shokat, K. Tags: Small Molecule Therapeutics Source Type: research

Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas.
Abstract The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed using chloroquine and Beclin 1 siRNA. Surgical specimens were examined for Beclin 1 protein expression by immunohistochemistry. The correlations between the loss of Beclin 1 expression and clinicopathological characteristics, prognosis and chemosensitivity were investigated. Inhibition of autophagy by chloroquin...
Source: International Journal of Oncology - October 6, 2015 Category: Cancer & Oncology Authors: Katagiri H, Nakayama K, Razia S, Nakamura K, Sato E, Ishibashi T, Ishikawa M, Iida K, Ishikawa N, Otsuki Y, Nakayama S, Kyo S Tags: Int J Oncol Source Type: research

A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation
Background: Ovarian cancer is now recognized as a number of distinct diseases primarily defined by histological subtype. Both clear cell ovarian carcinomas (CCC) and ovarian endometrioid carcinomas (EC) may arise from endometriosis and frequently harbor mutations in the ARID1A tumor suppressor gene. We studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC. Methods: Immunohistochemistry (IHC) for BAF250a expression was performed on 127 chemotherapy-naive ovarian carcinomas (33...
Source: BMC Cancer - February 22, 2014 Category: Cancer & Oncology Authors: Kimberly WiegandBryan HennessySamuel LeungYemin WangZhenlin JuMollianne McGahrenSteve KallogerSarah FinlaysonKatherine Stemke-HaleYiling LuFan ZhangMichael AnglesioBlake GilksGordon MillsDavid HuntsmanMark Carey Source Type: research