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Review
. 2019 Sep;84(3):487-499.
doi: 10.1007/s00280-019-03905-3. Epub 2019 Jul 15.

Cytochrome P450 3A4, 3A5, and 2C8 expression in breast, prostate, lung, endometrial, and ovarian tumors: relevance for resistance to taxanes

Maarten van Eijk  1 , René J Boosman  2 , Alfred H Schinkel  3 , Alwin D R Huitema  2   4 , Jos H Beijnen  2   3   5
Affiliations
Review

Cytochrome P450 3A4, 3A5, and 2C8 expression in breast, prostate, lung, endometrial, and ovarian tumors: relevance for resistance to taxanes

Maarten van Eijk et al. Cancer Chemother Pharmacol. 2019 Sep.

Abstract

Enzymes of the cytochrome P450 (CYP) subfamily 3A and 2C play a major role in the metabolism of taxane anticancer agents. While their function in hepatic metabolism of taxanes is well established, expression of these enzymes in solid tumors may play a role in the in situ metabolism of drugs as well, potentially affecting the intrinsic taxane susceptibility of these tumors. This article reviews the available literature on intratumoral expression of docetaxel- and paclitaxel-metabolizing enzymes in mammary, prostate, lung, endometrial, and ovarian tumors. Furthermore, the clinical implications of the intratumoral expression of these enzymes are reviewed and the potential of concomitant treatment with protease inhibitors (PIs) as a method to inhibit CYP3A4-mediated metabolism is discussed.

Keywords: CYP; Docetaxel; Intratumoral; Paclitaxel; Ritonavir.

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Conflict of interest statement

Jos Beijnen is a (part-time) employee and shareholder of Modra Pharmaceuticals, and (partly) holds a patent on oral taxane formulations. The other authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Chemical structures of the taxanes: a docetaxel and b paclitaxel
See this image and copyright information in PMC

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