Systematic identification of genomic markers of drug sensitivity in cancer cells.
- Garnett, M.J.
- Edelman, E.J.
- Heidorn, S.J.
- Greenman, C.D.
- Dastur, A.
- Lau, K.W.
- Greninger, P.
- Thompson, I.R.
- Luo, X.
- Soares, J.
- Liu, Q.
- Iorio, F.
- Surdez, D.
- Chen, L.
- Milano, R.J.
- Bignell, G.R.
- Tam, A.T.
- Davies, H.
- Stevenson, J.A.
- Barthorpe, S.
- Lutz, S.R.
- Kogera, F.
- Lawrence, K.
- McLaren-Douglas, A.
- Mitropoulos, X.
- Mironenko, T.
- Thi, H.
- Richardson, L.
- Zhou, W.
- Jewitt, F.
- Zhang, T.
- O'Brien, P.
- Boisvert, J.L.
- Price, S.
- Hur, W.
- Yang, W.
- Deng, X.
- Butler, A.
- Choi, H.G.
- Chang, J.W.
- Baselga, J.
- Stamenkovic, I.
- Engelman, J.A.
- Sharma, S.V.
- Delattre, O.
- Saez-Rodriguez, J.
- Gray, N.S.
- Settleman, J.
- Futreal, P.A.
- Haber, D.A.
- Stratton, M.R.
- Ramaswamy, S.
- McDermott, U.
- Benes, C.H.
DOIAbstract
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associat...
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