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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2017: 3.556

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

Online
ISSN
1437-4331
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Volume 40, Issue 9

Issues

Overcoming Multidrug Resistance in Taxane Chemotherapy

Raphaël Geney / Ioana Maria Ungureanu / Dansu Li / Iwao Ojima
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/CCLM.2002.161

Abstract

Paclitaxel (Taxol®) and docetaxel (Taxotère®) are currently two of the most important anticancer drugs in cancer chemotherapy. However, clinical treatment with these taxane agents often encounters undesirable side effects and multidrug resistance (MDR) caused by overexpression of P-glycoprotein (Pgp). Photoaffinity labeling of Pgp using photoreactive radiolabeled paclitaxel analogs along with molecular modeling has revealed a unique binding region for paclitaxel on the C-terminal half of Pgp. Highly efficient taxane-based MDR reversal agents (TRAs) have been developed. Extensive structure-activity relationship (SAR) studies have led to the development of new generation taxanes that possess 2–3 orders of magnitude higher potencies against human cancer cell lines expressing the MDR phenotype. One of these taxanes, SB-T-110131 (IDN5109, BAY59-8862), exhibits excellent activity against a variety of drug-sensitive and drug-resistant cancer cell lines as well as human tumor xenografts in mice. This taxane is orally active with excellent bioavailability, and is currently undergoing phase II human clinical trials. Novel taxane-antibody immunoconjugates have shown very promising results for tumor-specific delivery and release of an extremely cytotoxic taxane, wherein epidermal growth factor receptor is used as the specific antigen on the tumor surface of human squamous cancer xenograft in SCID mice.

About the article

Published Online: 2005-06-01

Published in Print: 2002-09-24


Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 40, Issue 9, Pages 918–925, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2002.161.

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