Cytochrome P450 3A4, 3A5, and 2C8 Expression in Breast, Prostate, Lung, Endometrial, and Ovarian Tumors: Relevance for Resistance to Taxanes

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 2019 Jul 17

PMID 31309254

Citations 36

Authors

Maarten van Eijk

Rene J Boosman

Alfred H Schinkel

Alwin D R Huitema

Jos H Beijnen

Affiliations

Soon will be listed here.

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.

Citing Articles

Structural Characterization of Heat Shock Protein 90β and Molecular Interactions with Geldanamycin and Ritonavir: A Computational Study.

Lima C, Antunes D, Caffarena E, Carels N Int J Mol Sci. 2024; 25(16).

PMID: 39201468 PMC: 11354266. DOI: 10.3390/ijms25168782.

Key genes and molecular mechanisms related to Paclitaxel Resistance.

Alalawy A Cancer Cell Int. 2024; 24(1):244.

PMID: 39003454 PMC: 11245874. DOI: 10.1186/s12935-024-03415-0.

Role of Cytochrome P450 3A4 in Cancer Drug Resistance: Challenges and Opportunities.

Pandey S, Verma S, Upreti S, Mishra A, Yadav N, Dwivedi-Agnihotri H Curr Drug Metab. 2024; 25(4):235-247.

PMID: 38984579 DOI: 10.2174/0113892002312369240703102215.

The deregulation of arachidonic acid metabolism in ovarian cancer.

Xia Q, Gao W, Yang J, Xing Z, Ji Z Front Oncol. 2024; 14:1381894.

PMID: 38764576 PMC: 11100328. DOI: 10.3389/fonc.2024.1381894.

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells.

Sanchez Y, Vasquez Callejas M, Miret N, Rolandelli G, Costas C, Randi A Explor Target Antitumor Ther. 2024; 5(2):278-295.

PMID: 38745771 PMC: 11090688. DOI: 10.37349/etat.2024.00218.

References

Yokose T, Doy M, Taniguchi T, Shimada T, Kakiki M, Horie T . Immunohistochemical study of cytochrome P450 2C and 3A in human non-neoplastic and neoplastic tissues. Virchows Arch. 1999; 434(5):401-11. DOI: 10.1007/s004280050359. View

Klose T, Blaisdell J, Goldstein J . Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. J Biochem Mol Toxicol. 1999; 13(6):289-95. DOI: 10.1002/(sici)1099-0461(1999)13:6<289::aid-jbt1>3.0.co;2-n. View

Goodwin B, Hodgson E, Liddle C . The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol. 1999; 56(6):1329-39. DOI: 10.1124/mol.56.6.1329. View

Traunecker H, Stevens M, Kerr D, Ferry D . The acridonecarboxamide GF120918 potently reverses P-glycoprotein-mediated resistance in human sarcoma MES-Dx5 cells. Br J Cancer. 1999; 81(6):942-51. PMC: 2362940. DOI: 10.1038/sj.bjc.6690791. View

Crown J, OLeary M . The taxanes: an update. Lancet. 2000; 355(9210):1176-8. DOI: 10.1016/S0140-6736(00)02074-2. View

Verschraegen C, Sittisomwong T, Kudelka A, Guedes E, Steger M, Vincent M . Docetaxel for patients with paclitaxel-resistant Müllerian carcinoma. J Clin Oncol. 2000; 18(14):2733-9. DOI: 10.1200/JCO.2000.18.14.2733. View

Synold T, Dussault I, Forman B . The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med. 2001; 7(5):584-90. DOI: 10.1038/87912. View

Fujitaka K, Oguri T, Isobe T, Fujiwara Y, Kohno N . Induction of cytochrome P450 3A4 by docetaxel in peripheral mononuclear cells and its expression in lung cancer. Cancer Chemother Pharmacol. 2001; 48(1):42-6. DOI: 10.1007/s002800100291. View

Zunino F, Cassinelli G, Polizzi D, Perego P . Molecular mechanisms of resistance to taxanes and therapeutic implications. Drug Resist Updat. 2001; 2(6):351-357. DOI: 10.1054/drup.1999.0108. View

10.

Schmidt R, Baumann F, Hanschmann H, Geissler F, Preiss R . Gender difference in ifosfamide metabolism by human liver microsomes. Eur J Drug Metab Pharmacokinet. 2001; 26(3):193-200. DOI: 10.1007/BF03190396. View

11.

Finnstrom N, Bjelfman C, Soderstrom T, Smith G, Egevad L, Norlen B . Detection of cytochrome P450 mRNA transcripts in prostate samples by RT-PCR. Eur J Clin Invest. 2001; 31(10):880-6. DOI: 10.1046/j.1365-2362.2001.00893.x. View

12.

Iscan M, Klaavuniemi T, Coban T, Kapucuoglu N, Pelkonen O, Raunio H . The expression of cytochrome P450 enzymes in human breast tumours and normal breast tissue. Breast Cancer Res Treat. 2002; 70(1):47-54. DOI: 10.1023/a:1012526406741. View

13.

Miyoshi Y, Ando A, Takamura Y, Taguchi T, Tamaki Y, Noguchi S . Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer tissues. Int J Cancer. 2002; 97(1):129-32. DOI: 10.1002/ijc.1568. View

14.

Cresteil T, Monsarrat B, Dubois J, Sonnier M, Alvinerie P, Gueritte F . Regioselective metabolism of taxoids by human CYP3A4 and 2C8: structure-activity relationship. Drug Metab Dispos. 2002; 30(4):438-45. DOI: 10.1124/dmd.30.4.438. View

15.

Patterson L, Murray G . Tumour cytochrome P450 and drug activation. Curr Pharm Des. 2002; 8(15):1335-47. DOI: 10.2174/1381612023394502. View

16.

Suh J, Payvandi F, Edelstein L, Amenta P, Zong W, Gelinas C . Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells. Prostate. 2002; 52(3):183-200. DOI: 10.1002/pros.10082. View

17.

Koch I, Weil R, Wolbold R, Brockmoller J, Hustert E, Burk O . Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA. Drug Metab Dispos. 2002; 30(10):1108-14. DOI: 10.1124/dmd.30.10.1108. View

18.

Martinez C, Garcia-Martin E, Pizarro R, Agundez J . Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy. Br J Cancer. 2002; 87(6):681-6. PMC: 2364247. DOI: 10.1038/sj.bjc.6600494. View

19.

Blanco J, Edick M, Hancock M, Winick N, Dervieux T, Amylon M . Genetic polymorphisms in CYP3A5, CYP3A4 and NQO1 in children who developed therapy-related myeloid malignancies. Pharmacogenetics. 2002; 12(8):605-11. DOI: 10.1097/00008571-200211000-00004. View

20.

Sarkar M, Vadlamuri V, Ghosh S, Glover D . Expression and cyclic variability of CYP3A4 and CYP3A7 isoforms in human endometrium and cervix during the menstrual cycle. Drug Metab Dispos. 2002; 31(1):1-6. DOI: 10.1124/dmd.31.1.1. View