Transport of topoisomerase I inhibitors by the breast cancer resistance protein - Potential clinical implications

JHM Schellens*, M Maliepaard, RJ Scheper, GL Scheffer, JW Jonker, JW Smit, JH Beijnen, AH Schinkel

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

106 Citations (Scopus)

Abstract

The multidrug resistance protein BCRP (breast cancer resistance protein) is a member of the ATP-binding cassette family of drug transporters. Overexpression of BCRP caused by exposure of cells to mitoxantrone (MX) or doxorubicin/verapamil resulted in a resistance pattern that is different from what is generally seen in the case of P-glycoprotein and MRP1 overexpression. Recently, the BCRP gene has been described in ovarian, breast, colon, and gastric cancer and fibrosarcoma cell lines. Our human tumor cells T8 and MX3, derived from the ovarian cancer cell line IGROV1 by stepwise increased exposure to topotecan and MX, are resistant to topotecan, CPT11, SN38, and 9-aminocamptothecin as well as MX. Increased energy-dependent efflux of affected drugs was noted. BCRP is a very efficient transporter of topotecan. Our recent studies, using the monoclonal antibody (mAb) BXP34, revealed that BCRP is located in the plasma membrane of the T8 and MX3 cell lines. Preliminary results of staining of human tumor cells showed low or absent levels of BCRP in a panel of solid tumors and acute myeloid leukemia cells.

Original languageEnglish
Title of host publicationCAMPTOTHECINS: UNFOLDING THEIR ANTICANER POTENTIAL
EditorsJG Liehr, BC Giovanella, CF Verschaegen
Place of PublicationNEW YORK
PublisherNew York Academy of Sciences
Pages188-194
Number of pages7
ISBN (Print)1-57331-291-6
Publication statusPublished - 2000
EventConference on the Camptothecins - Unfolding their Anticancer Potential - ARLINGTON, United Kingdom
Duration: 17-Mar-200020-Mar-2000

Publication series

NameANNALS OF THE NEW YORK ACADEMY OF SCIENCES
PublisherNEW YORK ACAD SCIENCES
Volume922
ISSN (Print)0077-8923

Conference

ConferenceConference on the Camptothecins - Unfolding their Anticancer Potential
CountryUnited Kingdom
Period17/03/200020/03/2000

Keywords

  • ENABLES ORAL-THERAPY
  • MULTIDRUG-RESISTANCE
  • P-GLYCOPROTEIN
  • CYCLOSPORINE-A
  • GENE
  • PACLITAXEL
  • TOPOTECAN
  • BIOAVAILABILITY
  • CELLS
  • OVEREXPRESSION

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