Increasing drug efficiency and reducing drug overall toxicity are two of the main goals of today`s drug chemotherapy of cancer. In general this could be achieved by searching new ways for selective active drug accumulation in cancer cells by manipulating local drug metabolism or delivery. In this short review, on the basis of the main directions described by McFadyen et al. (Mol Cancer Ther 2004; 3(3): 363-371), new data is reported for localization and expression of cytochrome P450 enzymes in human tumors, development of cytochrome P450-based and gene-directed enzyme activated prodrugs, antisense-based P450 and immune-based therapy, cytochrome P450 polymorphism in development of anticancer drugs. New discoveries of molecular biology of cancer give us hope for more successful development of modern cancer chemotherapy. Biomed Rev 2017; 28: 120-124.
Keywords: cytochrome P450 isoforms, cancer cells, drug metabolism, drug delivery
McFadyen MC, Melvin WT, Murray GI. Cytochrome P450 enzymes: novel options for cancer therapeutics. Mol Cancer Ther 2004; 3(3): 363-371.
Bruno RD, Njar VC. Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug development. Bioorg Med Chem 2007; 15(15): 5047-5060. [DOI:10.1016/j.bmc.2007.05.046]
Leclerc J, Tournel G, Courcot-Ngoubo Ngangue E, Pottier N, Lafitte J-J, Jaillard S, Mensier E, et al. Profiling gene expression of whole cytochrome P450 superfamily in human bronchial and peripheral lung tissues: Differential expression in non-small cell lung cancers. Biochimie 2010; 92(3): 292-306. [DOI: 10.1016/j.biochi.2009.12.007]
McFadyen MC, Melvin WT, Murray GI. Cytochrome P450 CYP1B1 activity in renal cell carcinoma. Br J Cancer 2004; 91(5): 966-971. [DOI: 10.1038/sj.bjc.6602053]
Saini S, Hirata H, Majid S, Dahiya R. Functional significance of cytochrome P450 1B1 in endometrial carcinogenesis. Cancer Res 2009; 69(17): 7038-7045. [DOI:10.1158/0008-5472.CAN-09-1691]
Karlgren M, Gomez A, Stark K, Svard J, Rodriguez-Antona C, Oliw E, Bernal ML, et al. Tumor-specific expression of the novel cytochrome P450 enzyme, CYP2W1. Biochem Biophys Res Commun 2006; 341(2): 451-458. [DOI: 10.1016/j.bbrc.2005.12.200]
McFadyen MC, Murray GI. Cytochrome P450 1B1: a novel anticancer therapeutic target. Future Oncol 2005; 1(2): 259-263. [DOI: 10.1517/14796694.1.2.259]
Oyama T, Kagawa N, Kunugita N, Kitagawa K, Ogawa M, Yamaguchi T, Suzuki R, et al. Expression of cytochrome P450 in tumor tissues and its association with cancer development. Front Biosci 2004; 9(1967-1976. [DOI: 10.2741/1378]
Tokizane T, Shiina H, Igawa M, Enokida H, Urakami S, Kawakami T, Ogishima T, et al. Cytochrome P450 1B1 is overexpressed and regulated by hypomethylation in prostate cancer. Clin Cancer Res 2005; 11(16): 5793-5801. [DOI: 10.1158/1078-0432.CCR-04-2545]
Wen X, Walle T. Cytochrome P450 1B1, a novel chemopreventive target for benzo[α]pyrene-initiated human esophageal cancer. Cancer Letters 2007; 246(1): 109-114. [DOI: 10.1016/j.canlet.2006.02.003]
D`Uva G, Baci D, Albini A, Noonan DM. Cancer chemoprevention revisited: Cytochrome P450 family 1B1 as a target in the tumor and the microenvironment. Cancer Treatment Reviews 2018; 63 (Supplement C): 1-18. [DOI: 10.1016/j.ctrv.2017.10.013]
Murray GI, Patimalla S, Stewart KN, Miller ID, Heys SD. Profiling the expression of cytochrome P450 in breast cancer. Histopathology 2010; 57(2): 202-211. [DOI: 10.1111/j.1365-2559.2010.03606.x]
Gomez A, Karlgren M, Edler D, Bernal ML, Mkrtchian S, Ingelman-Sundberg M. Expression of CYP2W1 in colon tumors: regulation by gene methylation. Pharmacogenomics 2007; 8(10): 1315-1325. [DOI: 10.2217/14622416.8.10.1315]
Edler D, Stenstedt K, Ohrling K, Hallstrom M, Karlgren M, Ingelman-Sundberg M, Ragnhammar P. The expression of the novel CYP2W1 enzyme is an independent prognostic factor in colorectal cancer - a pilot study. Eur J Cancer 2009; 45(4): 705-712. [DOI: 10.1016/j.ejca.2008.11.031]
Sutherland M, Gill JH, Loadman PM, Laye JP, Sheldrake HM, Illingworth NA, Alandas MN, et al. Antitumor Activity of a Duocarmycin Analogue Rationalized to Be Metabolically Activated by Cytochrome P450 1A1 in Human Transitional Cell Carcinoma of the Bladder. Molecular Cancer Therapeutics 2013; 12(1): 27-37. [DOI: 10.1158/1535-7163.mct-12-0405]
Chen C, Wei X, Rao X, Wu J, Yang S, Chen F, Ma D, et al. Cytochrome P450 2J2 Is Highly Expressed in Hematologic Malignant Diseases and Promotes Tumor Cell Growth. Journal of Pharmacology and Experimental Therapeutics 2011; 336(2): 344-355. [DOI: 10.1124/jpet.110.174805]
Lane CS, Nisar S, Griffiths WJ, Fuller BJ, Davidson BR, Hewes J, Welham KJ, et al. Identification of cytochrome P450 enzymes in human colorectal metastases and the surrounding liver: a proteomic approach. Eur J Cancer 2004; 40(14): 2127-2134. [DOI: 10.1016/j.ejca.2004.04.029]
Kivisto KT, Kroemer HK, Eichelbaum M. The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions. Br J Clin Pharmacol 1995; 40(6): 523-530. [DOI: 10.1111/j.1365-2125.1995.tb05796.x]
Rooseboom M, Commandeur JN, Vermeulen NP. Enzyme-catalyzed activation of anticancer prodrugs. Pharmacol Rev 2004; 56(1): 53-102. [DOI: 10.1124/pr.56.1.3]
Ortiz de Montellano PR. Cytochrome P450-activated prodrugs. Future Medicinal Chemistry 2013; 5(2): 213-228. [DOI: 10.4155/fmc.12.197]
Cai TB, Wang PG. Recent developments in anticancer nitric oxide donors. Expert Opinion on Therapeutic Patents 2004; 14(6): 849-857. [DOI: 10.1517/13543776.14.6.849]
Leong CO, Suggitt M, Swaine DJ, Bibby MC, Stevens MF, Bradshaw TD. In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles. Mol Cancer Ther 2004; 3(12): 1565-1575.
Loaiza-Pérez AI, Trapani V, Hose C, Singh SS, Trepel JB, Stevens MFG, Bradshaw TD, et al. Aryl Hydrocarbon Receptor Mediates Sensitivity of MCF-7 Breast Cancer Cells to Antitumor Agent 2-(4-Amino-3-methylphenyl) Benzothiazole. Molecular Pharmacology 2002; 61(1): 13-19. [DOI: 10.1124/mol.61.1.13]
Mukherjee A, Martin SG. In vitro cytotoxicity of Phortress against colorectal cancer. Int J Oncol 2006; 29(5): 1287-1294. [DOI: 10.3892/ijo.29.5.1287]
Lu H, Waxman DJ. Antitumor activity of methoxymorpholinyl doxorubicin: potentiation by cytochrome P450 3A metabolism. Mol Pharmacol 2005; 67(1): 212-219. [DOI: 10.1124/mol.104.005371]
Potter GA, Patterson LH, Wanogho E, Perry PJ, Butler PC, Ijaz T, Ruparelia KC, et al. The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. Br J Cancer 2002; 86(5): 774-778. [DOI: 10.1038/sj.bjc.6600197]
Wolter F, Clausnitzer A, Akoglu B, Stein J. Piceatannol, a natural analog of resveratrol, inhibits progression through the S phase of the cell cycle in colorectal cancer cell lines. J Nutr 2002; 132(2): 298-302.
Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer 2011; 11(6): 393-410. [DOI: 10.1038/nrc3064]
Riddick DS, Lee C, Ramji S, Chinje EC, Cowen RL, Williams KJ, Patterson AV, et al. Cancer chemotherapy and drug metabolism. Drug Metab Dispos 2005; 33(8): 1083-1096. [DOI: 10.1124/dmd.105.004374]
McCarthy HO, Yakkundi A, McErlane V, Hughes CM, Keilty G, Murray M, Patterson LH, et al. Bioreductive GDEPT using cytochrome P450 3A4 in combination with AQ4N. Cancer Gene Therapy 2002; 10(40. [DOI: 10.1038/sj.cgt.7700522]
Lazzari P, Spiga M, Sani M, Zanda M, Fleming IN. KEMTUB012-NI2, a novel potent tubulysin analog that selectively targets hypoxic cancer cells and is potentiated by cytochrome p450 reductase downregulation. Hypoxia 2017; 5(45-59. [DOI: 10.2147/HP.S132832]
Zhang J, Kale V, Chen M. Gene-Directed Enzyme Prodrug Therapy. The AAPS Journal 2015; 17(1): 102-110. [DOI: 10.1208/s12248-014-9675-7]
Zhu Z, Mu Y, Qi C, Wang J, Xi G, Guo J, Mi R, et al. CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro. Int J Mol Med 2015; 35(2): 340-348. [DOI: 10.3892/ijmm.2014.2041]
Paolini M, Poul L, Darmon A, Germain M, Pottier A, Levy L, Vibert E. A new opportunity for nanomedicines: Micellar cytochrome P450 inhibitors to improve drug efficacy in a cancer therapy model. Nanomedicine: Nanotechnology, Biology and Medicine 2017; 13(5): 1715-1723. [DOI: 10.1016/j.nano.2017.03.006]
Rodriguez-Antona C, Gomez A, Karlgren M, Sim SC, Ingelman-Sundberg M. Molecular genetics and epigenetics of the cytochrome P450 gene family and its relevance for cancer risk and treatment. Human Genetics 2010; 127(1): 1-17. [DOI: 10.1007/s00439-009-0748-0]
Purnapatre K, Khattar SK, Saini KS. Cytochrome P450s in the development of target-based anticancer drugs. Cancer Lett 2008; 259(1): 1-15. [DOI: 10.1016/j.canlet.2007.10.024]
Mathijssen RH, van Schaik RH. Genotyping and phenotyping cytochrome P450: perspectives for cancer treatment. Eur J Cancer 2006; 42(2): 141-148. [DOI: 10.1016/j.ejca.2005.08.035]
Rodriguez-Antona C, Ingelman-Sundberg M. Cytochrome P450 pharmacogenetics and cancer. Oncogene 2006; 25(11): 1679-1691. [DOI: 10.1038/sj.onc.1209377]
Scripture CD, Sparreboom A, Figg WD. Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol 2005; 6(10): 780-789. [DOI: 10.1016/S1470-2045(05)70388-0]