Statistical tests have been used in to show that genetic mutations can be predictive of the drug sensitivity in non small cell lung cancers but the classification rates of these predictors based on indi vidual selleck inhibitor mutations for the aberrant samples are still low. For specific diseases, some mutations have been able to predict the patients that will not respond to particular therapies, for instance reports a success rate of 87% in predicting non responders to anti EGFR monoclonal antibodies using the mutational status of KRAS, BRAF, PIK3CA and PTEN. The prediction of tumor sensitivity to drugs has also been approached as a classification prob lem using gene expression profiles. In, gene expression profiles are used to predict the binarized efficacy of a drug over a cell line with the accuracy of the designed classi fiers ranging from 64% to 92%.

In, a co expression extrapolation approach is used to predict the binarized drug sensitivity in data points outside the train ing set with an accuracy of around 75%. In, a Random Forest based ensemble approach was used for predic tion of drug sensitivity and achieved an R2 value of 0. 39 between the predicted IC50s and experimental IC50s. Supervised machine learning approaches using genomic signatures achieved a specificity and sensitivity of higher than 70% for prediction of drug response in. Tumor sensitivity prediction has also been considered as a drug induced topology alteration using phospho proteomic signals and prior biological knowledge of a generic pathway and a molecular tumor profile based prediction.

Most interestingly, in the recent cancer cell line ency clopedia study, the authors characterize a large set of cell lines with numerous associated data measurement sets, gene and protein expression pro files, mutation profiles, methylation data along with the response of around 500 of these cells lines across 24 anti cancer drugs. One of the goals of the study was to enable predictive modeling of cancer drug sensitivity. For gener ating predictive models, the authors considered regression based analysis across input features of gene and protein expression profiles, mutation profiles and methylation data. The performance of the predictive models using 10 fold cross validation ranged between 0. 1 to 0. 8. In particular, the correlation coefficient for prediction of sensitivity using genomic signatures for the drug Erlotinib across 450 cell lines was 0. 35. Erlotinib is a commonly used tryosine kinase inhibitor selected primarily as an EGFR inhibitor. However, studies have shown that these tar geted drugs often have numerous side Carfilzomib targets that can play significant roles in the effectiveness of the inhibitor drugs.