Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers

Efficacies, toxicities, and resistance mechanisms of chemotherapy drugs, such as oxaliplatin and 5-fluorouracil (5-FU), vary widely among various categories and subcategories of colon cancers. By understanding the differences in the drug efficacy and resistance at the level of protein–protein networ...

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Main Authors: Swarnendu Tripathi, Louiza Belkacemi, Margaret S. Cheung, Rathindra N. Bose
Format: Article
Language:English
Published: SAGE Publishing 2016-01-01
Series:Cancer Informatics
Online Access:https://doi.org/10.4137/CIN.S34506
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author Swarnendu Tripathi
Louiza Belkacemi
Margaret S. Cheung
Rathindra N. Bose
author_facet Swarnendu Tripathi
Louiza Belkacemi
Margaret S. Cheung
Rathindra N. Bose
author_sort Swarnendu Tripathi
collection DOAJ
description Efficacies, toxicities, and resistance mechanisms of chemotherapy drugs, such as oxaliplatin and 5-fluorouracil (5-FU), vary widely among various categories and subcategories of colon cancers. By understanding the differences in the drug efficacy and resistance at the level of protein–protein networks, we identified the correlation between the drug activity of oxaliplatin/5-FU and gene variations from the US National Cancer Institute-60 human cancer cell lines. The activity of either of these drugs is correlated with specific amino acid variant(s) of KRAS and other genes from the signaling pathways of colon cancer progression. We also discovered that the activity of a non-DNA-binding novel platinum drug, phosphaplatin, is comparable with oxaliplatin and 5-FU when it was tested against colon cancer cell lines. Our strategy that combines the knowledge from pharmacogenomics across cell lines with the molecular information from specific cancer cells is beneficial for predicting the outcome of a possible combination therapy for personalized treatment.
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spelling doaj.art-1ed70e4454214fa59f24435f32dfc2872022-12-21T22:46:01ZengSAGE PublishingCancer Informatics1176-93512016-01-011510.4137/CIN.S34506Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon CancersSwarnendu Tripathi0Louiza Belkacemi1Margaret S. Cheung2Rathindra N. Bose3Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.Department of Biology & Biochemistry, University of Houston, Houston, TX, USA.Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.Department of Biology & Biochemistry, University of Houston, Houston, TX, USA.Efficacies, toxicities, and resistance mechanisms of chemotherapy drugs, such as oxaliplatin and 5-fluorouracil (5-FU), vary widely among various categories and subcategories of colon cancers. By understanding the differences in the drug efficacy and resistance at the level of protein–protein networks, we identified the correlation between the drug activity of oxaliplatin/5-FU and gene variations from the US National Cancer Institute-60 human cancer cell lines. The activity of either of these drugs is correlated with specific amino acid variant(s) of KRAS and other genes from the signaling pathways of colon cancer progression. We also discovered that the activity of a non-DNA-binding novel platinum drug, phosphaplatin, is comparable with oxaliplatin and 5-FU when it was tested against colon cancer cell lines. Our strategy that combines the knowledge from pharmacogenomics across cell lines with the molecular information from specific cancer cells is beneficial for predicting the outcome of a possible combination therapy for personalized treatment.https://doi.org/10.4137/CIN.S34506
spellingShingle Swarnendu Tripathi
Louiza Belkacemi
Margaret S. Cheung
Rathindra N. Bose
Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers
Cancer Informatics
title Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers
title_full Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers
title_fullStr Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers
title_full_unstemmed Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers
title_short Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers
title_sort correlation between gene variants signaling pathways and efficacy of chemotherapy drugs against colon cancers
url https://doi.org/10.4137/CIN.S34506
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