Dataset Information

In silico modeling predicts drug sensitivity of patient-derived cancer cells.

ABSTRACT:

Background

Glioblastoma (GBM) is an aggressive disease associated with poor survival. It is essential to account for the complexity of GBM biology to improve diagnostic and therapeutic strategies. This complexity is best represented by the increasing amounts of profiling ("omics") data available due to advances in biotechnology. The challenge of integrating these vast genomic and proteomic data can be addressed by a comprehensive systems modeling approach.

Methods

Here, we present an in silico model, where we simulate GBM tumor cells using genomic profiling data. We use this in silico tumor model to predict responses of cancer cells to targeted drugs. Initially, we probed the results from a recent hypothesis-independent, empirical study by Garnett and co-workers that analyzed the sensitivity of hundreds of profiled cancer cell lines to 130 different anticancer agents. We then used the tumor model to predict sensitivity of patient-derived GBM cell lines to different targeted therapeutic agents.

Results

Among the drug-mutation associations reported in the Garnett study, our in silico model accurately predicted ~85% of the associations. While testing the model in a prospective manner using simulations of patient-derived GBM cell lines, we compared our simulation predictions with experimental data using the same cells in vitro. This analysis yielded a ~75% agreement of in silico drug sensitivity with in vitro experimental findings.

Conclusions

These results demonstrate a strong predictability of our simulation approach using the in silico tumor model presented here. Our ultimate goal is to use this model to stratify patients for clinical trials. By accurately predicting responses of cancer cells to targeted agents a priori, this in silico tumor model provides an innovative approach to personalizing therapy and promises to improve clinical management of cancer.

SUBMITTER: Pingle SC

PROVIDER: S-EPMC4030016 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

In silico modeling predicts drug sensitivity of patient-derived cancer cells.

Pingle Sandeep C SC Sultana Zeba Z Pastorino Sandra S Jiang Pengfei P Mukthavaram Rajesh R Chao Ying Y Bharati Ila Sri IS Nomura Natsuko N Makale Milan M Abbasi Taher T Kapoor Shweta S Kumar Ansu A Usmani Shahabuddin S Agrawal Ashish A Vali Shireen S Kesari Santosh S

Journal of translational medicine 20140521

<h4>Background</h4>Glioblastoma (GBM) is an aggressive disease associated with poor survival. It is essential to account for the complexity of GBM biology to improve diagnostic and therapeutic strategies. This complexity is best represented by the increasing amounts of profiling ("omics") data available due to advances in biotechnology. The challenge of integrating these vast genomic and proteomic data can be addressed by a comprehensive systems modeling approach.<h4>Methods</h4>Here, we present ...[more]

PMID: 24884660

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Dataset Information

In silico modeling predicts drug sensitivity of patient-derived cancer cells.

Background

Methods

Results

Conclusions

Publications

In silico modeling predicts drug sensitivity of patient-derived cancer cells.

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