Cytochrome P450 family members in the personalized treatment of breast cancer

Abstract

Cytochrome P450 enzymes are responsible for the phase I metabolism of many drugs and xenobiotics several of them being procarcinogens and environmental toxins. Most of the cytochrome P450 enzymes’ functions have been studied in the liver but many reports have demonstrated expression of several cytochrome P450 family members in extra hepatic tissues. Whether the functions of these enzymes in the extra hepatic tissues are the same as those they exert in the liver is a question that has not been studied extensively. CYP1A1 and CYP1B1 catalyse the metabolic activation of several procarcinogens including the 17beta-estradiol (E2) by hydroxylating either the C-2 (CYP1A1) or C-4 (CYP1B1) positions leading to the generation of non-toxic (CYP1A1) or toxic (CYP1B1) metabolites. CYP1B1 is over-expressed in various malignant compared to normal tissues such as lung, kidney, breast, uterus and ovaries. This in combination with the fact that CYP1B1 generates toxic metabolites (4- hydroxyestradiol (4-OH E2)) raises the possibility that the ratio of the cellular levels of CYP1A1 and CYP1B1 might determine cancer progression or tumour suppression.

Date of Award	12 Sept 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jeffrey Penny (Co Supervisor) & Costas Demonacos (Main Supervisor)