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12 - Apoptosis and chemoresistance

from Part II - Cell biology and pathobiology

Published online by Cambridge University Press:  01 July 2010

By
Kirsteen H. Maclean  and
John L. Cleveland
Edited by
Ching-Hon Pui
Kirsteen H. Maclean
Affiliation:
Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
John L. Cleveland
Affiliation:
Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
Ching-Hon Pui
Affiliation:
St. Jude Children's Research Hospital, Memphis
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Summary

Introduction

The development of chemoresistance in tumors is a major obstacle in oncology, particularly in the treatment of acute myeloid leukemia. Resistance to therapy can be broad (multidrug resistance) and arise de novo, but is more frequently acquired following the relapse of disease in patients previously treated with chemotherapy. The chemoresistance phenotype can arise through several mechanisms including: (1) overexpression of the P-glycoprotein family of membrane transporters (MDR1, MRP, LRP), which decrease the intracellular levels of anticancer drugs; (2) changes in cellular enzymes that detoxify or metabolize drugs, such as dihydrofolate reductase and cytochrome p450 enzymes; and (3) changes in enzymes intimately involved in DNA repair, such as DNA topoisomerase II. A fourth and more general mechanism involves changes in the expression and/or activity of proteins that regulate apoptosis, an endogenous program of cell suicide that disassembles the cell when it has received damage or oncogenic insults. Given the number of regulators that feed into the apoptotic response, understanding this mechanism of resistance is now recognized as a significant challenge; however, targeting these regulators holds great promise of overcoming or bypassing drug resistance in relapsed cancer patients.

For many years, radiation treatment and chemotherapy were thought to cause irreparable metabolic or physical damage to cancer cells, resulting in cell necrosis.

Type
Chapter
Information
Childhood Leukemias , pp. 339 - 361
Publisher: Cambridge University Press
Print publication year: 2006

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  • Apoptosis and chemoresistance
    • By Kirsteen H. Maclean, Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA, John L. Cleveland, Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.013
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  • Apoptosis and chemoresistance
    • By Kirsteen H. Maclean, Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA, John L. Cleveland, Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.013
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  • Apoptosis and chemoresistance
    • By Kirsteen H. Maclean, Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA, John L. Cleveland, Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.013
Available formats
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