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A strategy for predicting the chemosensitivity of human cancers and
its application to drug discovery
Lee JK, Havaleshko DM, Cho H, Weinstein JN, Kaldjian EP, Karpovich J, Grimshaw A,
Theodorescu D.
Proc Natl Acad Sci U S A. 2007 Jul 31
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Abstract:
The U.S. National Cancer Institute has used a panel of 60 diverse human cancer cell lines (the NCI-60) to screen >100,000
chemical compounds for anticancer activity. However, not all important cancer types are included in the panel, nor are
drug responses of the panel predictive of clinical efficacy in patients. We asked, therefore, whether it would be possible
to extrapolate from that rich database (or analogous ones from other drug screens) to predict activity in cell types not
included or, for that matter, clinical responses in patients with tumors. We address that challenge by developing and
applying an algorithm we term "coexpression extrapolation" (COXEN). COXEN uses expression microarray data as a Rosetta
Stone for translating from drug activities in the NCI-60 to drug activities in any other cell panel or set of clinical
tumors. Here, we show that COXEN can accurately predict drug sensitivity of bladder cancer cell lines and clinical
responses of breast cancer patients treated with commonly used chemotherapeutic drugs. Furthermore, we used COXEN for
in silico screening of 45,545 compounds and identify an agent with activity against human bladder cancer.
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