Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

Publication: Research - peer-reviewJournal article – Annual report year: 2012

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@article{446d98d451844bb29862adef7f8dc742,
title = "Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data",
keywords = "Gene expression, Molecular structures, NCI60, Topoisomerase inhibitors, Chemosensitivity, Cancer",
publisher = "Pergamon",
author = "Peng Wan and Qiyuan Li and Larsen, {Jens Erik Pontoppidan} and Eklund, {Aron Charles} and Alexandr Parlesak and Olga Rigina and Nielsen, {Søren Jensby} and Fredrik Björkling and Jonsdottir, {Svava Osk}",
year = "2012",
doi = "10.1016/j.bmc.2011.11.019",
volume = "20",
number = "1",
pages = "167--176",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",

}

RIS

TY - JOUR

T1 - Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

A1 - Wan,Peng

A1 - Li,Qiyuan

A1 - Larsen,Jens Erik Pontoppidan

A1 - Eklund,Aron Charles

A1 - Parlesak,Alexandr

A1 - Rigina,Olga

A1 - Nielsen,Søren Jensby

A1 - Björkling,Fredrik

A1 - Jonsdottir,Svava Osk

AU - Wan,Peng

AU - Li,Qiyuan

AU - Larsen,Jens Erik Pontoppidan

AU - Eklund,Aron Charles

AU - Parlesak,Alexandr

AU - Rigina,Olga

AU - Nielsen,Søren Jensby

AU - Björkling,Fredrik

AU - Jonsdottir,Svava Osk

PB - Pergamon

PY - 2012

Y1 - 2012

N2 - The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333 compounds with reliable experimental half maximum growth inhibitions (GI50) values for 30 cell lines from the NCI60 data set and evaluated their growth inhibitory effect (chemosensitivity) with respect to tissue of origin. This was done by identifying natural clusters in the chemosensitivity data set and in a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively. The strong difference in gene expression between basal and luminal breast cancer cells was reflected clearly in the chemosensitivity data. Although most compounds in the data set were of low potency, high efficacy compounds that showed specificity with respect to tissue of origin could be found. Furthermore, eight potential topoisomerase II inhibitors were identified using a structural similarity search. Finally, a set of genes with expression profiles that were significantly correlated with anti-cancer drug activity was identified. Our study demonstrates that the combined data sets, which provide comprehensive information on drug activity and gene expression profiles of tumor cell lines studied, are useful for identifying potential new active compounds.

AB - The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333 compounds with reliable experimental half maximum growth inhibitions (GI50) values for 30 cell lines from the NCI60 data set and evaluated their growth inhibitory effect (chemosensitivity) with respect to tissue of origin. This was done by identifying natural clusters in the chemosensitivity data set and in a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively. The strong difference in gene expression between basal and luminal breast cancer cells was reflected clearly in the chemosensitivity data. Although most compounds in the data set were of low potency, high efficacy compounds that showed specificity with respect to tissue of origin could be found. Furthermore, eight potential topoisomerase II inhibitors were identified using a structural similarity search. Finally, a set of genes with expression profiles that were significantly correlated with anti-cancer drug activity was identified. Our study demonstrates that the combined data sets, which provide comprehensive information on drug activity and gene expression profiles of tumor cell lines studied, are useful for identifying potential new active compounds.

KW - Gene expression

KW - Molecular structures

KW - NCI60

KW - Topoisomerase inhibitors

KW - Chemosensitivity

KW - Cancer

U2 - 10.1016/j.bmc.2011.11.019

DO - 10.1016/j.bmc.2011.11.019

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 1

VL - 20

SP - 167

EP - 176

ER -