Prediction of broad spectrum resistance of tumors towards anticancer drugs

Publication type:
Journal article
Metadata:
Autoren
  • Thomas Efferth
  • V Badireenath Konkimalla
  • Yi-Fen Wang
  • Axel Sauerbrey
  • Silke Meinhardt
  • Felix Zintl
  • Juegen Mattern
  • Manfred Volm
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000254943600021&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1158/1078-0432.CCR-07-4525
Externe Identifier
  • Clarivate Analytics Document Solution ID: 287VC
  • PubMed Identifier: 18413831
ISSN
1078-0432
Ausgabe der Veröffentlichung
8
Zeitschrift
CLINICAL CANCER RESEARCH
Paginierung
2405 - 2412
Datum der Veröffentlichung
2008
Status
Published
Titel
Prediction of broad spectrum resistance of tumors towards anticancer drugs
Sub types
  • Article
Ausgabe der Zeitschrift
14

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title> <jats:p>Purpose: Drug resistance is a major obstacle in cancer chemotherapy. Although the statistical probability of therapeutic success is known for larger patient groups from clinical therapy trials, it is difficult to predict the individual response of tumors. The concept of individualized therapy aims to determine in vitro the drug response of tumors beforehand to choose effective treatment options for each individual patient.</jats:p> <jats:p>Experimental Design: We analyzed the cross-resistance profiles of different tumor types (cancers of lung, breast, and colon, and leukemia) towards drugs from different classes (anthracyclines, antibiotics, Vinca alkaloids, epipodophyllotoxins, antimetabolites, and alkylating agents) by nucleotide incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Hierarchical cluster analysis and COMPARE analyses were applied.</jats:p> <jats:p>Results: Tumors exert broad resistance profiles, e.g., tumors resistant to one drug tend to also be resistant to other drugs, whereas sensitive tumors reveal sensitivity towards many drugs. Interestingly, the broad spectrum resistance phenotype could reliably be predicted by doxorubicin alone. Expression of the ATP-binding cassette transporter P-glycoprotein (ABCB1, MDR1) and the proliferative activity of tumors were identified as underlying mechanisms of broad spectrum resistance. To find novel compounds with activity against drug-resistant tumors, a database with 2,420 natural products was screened for compounds acting independent of P-glycoprotein and the proliferative state of tumor cells.</jats:p> <jats:p>Conclusions: Tumors exert cross-resistance profiles much broader than the classical multidrug resistance phenotype. Broad spectrum resistance can be predicted by doxorubicin due to the multifactorial mode of action of this drug. Novel cytotoxic compounds from natural resources might be valuable tools for strategies to bypass broad spectrum resistance.</jats:p>
Autoren
  • Thomas Efferth
  • V Badireenath Konkimalla
  • Yi-Fen Wang
  • Axel Sauerbrey
  • Silke Meinhardt
  • Felix Zintl
  • Jürgen Mattern
  • Manfred Volm
DOI
10.1158/1078-0432.ccr-07-4525
eISSN
1557-3265
ISSN
1078-0432
Ausgabe der Veröffentlichung
8
Zeitschrift
Clinical Cancer Research
Sprache
en
Online publication date
2008
Paginierung
2405 - 2412
Datum der Veröffentlichung
2008
Status
Published
Herausgeber
American Association for Cancer Research (AACR)
Herausgeber URL
http://dx.doi.org/10.1158/1078-0432.ccr-07-4525
Datum der Datenerfassung
2022
Titel
Prediction of Broad Spectrum Resistance of Tumors towards Anticancer Drugs
Ausgabe der Zeitschrift
14

Data source: Crossref

Abstract
<h4>Purpose</h4>Drug resistance is a major obstacle in cancer chemotherapy. Although the statistical probability of therapeutic success is known for larger patient groups from clinical therapy trials, it is difficult to predict the individual response of tumors. The concept of individualized therapy aims to determine in vitro the drug response of tumors beforehand to choose effective treatment options for each individual patient.<h4>Experimental design</h4>We analyzed the cross-resistance profiles of different tumor types (cancers of lung, breast, and colon, and leukemia) towards drugs from different classes (anthracyclines, antibiotics, Vinca alkaloids, epipodophyllotoxins, antimetabolites, and alkylating agents) by nucleotide incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Hierarchical cluster analysis and COMPARE analyses were applied.<h4>Results</h4>Tumors exert broad resistance profiles, e.g., tumors resistant to one drug tend to also be resistant to other drugs, whereas sensitive tumors reveal sensitivity towards many drugs. Interestingly, the broad spectrum resistance phenotype could reliably be predicted by doxorubicin alone. Expression of the ATP-binding cassette transporter P-glycoprotein (ABCB1, MDR1) and the proliferative activity of tumors were identified as underlying mechanisms of broad spectrum resistance. To find novel compounds with activity against drug-resistant tumors, a database with 2,420 natural products was screened for compounds acting independent of P-glycoprotein and the proliferative state of tumor cells.<h4>Conclusions</h4>Tumors exert cross-resistance profiles much broader than the classical multidrug resistance phenotype. Broad spectrum resistance can be predicted by doxorubicin due to the multifactorial mode of action of this drug. Novel cytotoxic compounds from natural resources might be valuable tools for strategies to bypass broad spectrum resistance.
Addresses
  • German Cancer Research Center, University of Heidelberg, Heidelberg, Germany. t.efferth@dkfz.de
Autoren
  • Thomas Efferth
  • Thomas Efferth
  • V Badireenath Konkimalla
  • Yi-Fen Wang
  • Axel Sauerbrey
  • Silke Meinhardt
  • Felix Zintl
  • Jürgen Mattern
  • Manfred Volm
DOI
10.1158/1078-0432.ccr-07-4525
eISSN
1557-3265
Externe Identifier
  • PubMed Identifier: 18413831
Open access
false
ISSN
1078-0432
Ausgabe der Veröffentlichung
8
Zeitschrift
Clinical cancer research : an official journal of the American Association for Cancer Research
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Neoplasms
  • Antineoplastic Agents
  • Medicine, Chinese Traditional
  • Cluster Analysis
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
Sprache
eng
Medium
Print
Paginierung
2405 - 2412
Datum der Veröffentlichung
2008
Status
Published
Datum der Datenerfassung
2008
Titel
Prediction of broad spectrum resistance of tumors towards anticancer drugs.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
14

Data source: Europe PubMed Central

Abstract
PURPOSE: Drug resistance is a major obstacle in cancer chemotherapy. Although the statistical probability of therapeutic success is known for larger patient groups from clinical therapy trials, it is difficult to predict the individual response of tumors. The concept of individualized therapy aims to determine in vitro the drug response of tumors beforehand to choose effective treatment options for each individual patient. EXPERIMENTAL DESIGN: We analyzed the cross-resistance profiles of different tumor types (cancers of lung, breast, and colon, and leukemia) towards drugs from different classes (anthracyclines, antibiotics, Vinca alkaloids, epipodophyllotoxins, antimetabolites, and alkylating agents) by nucleotide incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Hierarchical cluster analysis and COMPARE analyses were applied. RESULTS: Tumors exert broad resistance profiles, e.g., tumors resistant to one drug tend to also be resistant to other drugs, whereas sensitive tumors reveal sensitivity towards many drugs. Interestingly, the broad spectrum resistance phenotype could reliably be predicted by doxorubicin alone. Expression of the ATP-binding cassette transporter P-glycoprotein (ABCB1, MDR1) and the proliferative activity of tumors were identified as underlying mechanisms of broad spectrum resistance. To find novel compounds with activity against drug-resistant tumors, a database with 2,420 natural products was screened for compounds acting independent of P-glycoprotein and the proliferative state of tumor cells. CONCLUSIONS: Tumors exert cross-resistance profiles much broader than the classical multidrug resistance phenotype. Broad spectrum resistance can be predicted by doxorubicin due to the multifactorial mode of action of this drug. Novel cytotoxic compounds from natural resources might be valuable tools for strategies to bypass broad spectrum resistance.
Autoren
  • Thomas Efferth
  • V Badireenath Konkimalla
  • Yi-Fen Wang
  • Axel Sauerbrey
  • Silke Meinhardt
  • Felix Zintl
  • Jürgen Mattern
  • Manfred Volm
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/18413831
DOI
10.1158/1078-0432.CCR-07-4525
ISSN
1078-0432
Ausgabe der Veröffentlichung
8
Zeitschrift
Clin Cancer Res
Schlüsselwörter
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Cell Line, Tumor
  • Cell Proliferation
  • Cluster Analysis
  • Drug Resistance, Neoplasm
  • Humans
  • Medicine, Chinese Traditional
  • Neoplasms
Sprache
eng
Country
United States
Paginierung
2405 - 2412
PII
14/8/2405
Datum der Veröffentlichung
2008
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2008
Titel
Prediction of broad spectrum resistance of tumors towards anticancer drugs.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
14

Data source: PubMed

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