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

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

Volume: 25 Issue: 4

Author(s): Swaroop Kumar Pandey*, Sona Verma, Shobha Upreti, Anuja Mishra, Neha Yadav and Hemlata Dwivedi-Agnihotri*

Affiliation:

• Department of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura, 281406, India

• Department of Biophysics, University of Delhi, South Campus, New Delhi-110021, India

Keywords: CYPs, CYP3A4, drug metabolism, drug efflux, drug resistance, cancer.

Abstract: One of the biggest obstacles to the treatment of diseases, particularly serious conditions like cancer, is therapeutic resistance. The process of drug resistance is influenced by a number of important variables, including MDR genes, drug efflux, low-quality medications, inadequate dosage, etc. Drug resistance must be addressed, and new combinations based on the pharmacokinetics/pharmacodynamics (PK-PD) characteristics of the partner pharmaceuticals must be developed in order to extend the half-lives of already available medications. The primary mechanism of drug elimination is hepatic biotransformation of medicines by cytochrome P450 (CYP) enzymes; of these CYPs, CYP3A4 makes up 30–40% of all known cytochromes that metabolize medications. Induction or inhibition of CYP3A4-mediated metabolism affects the pharmacokinetics of most anticancer drugs, but these details are not fully understood and highlighted because of the complexity of tumor microenvironments and various influencing patient related factors. The involvement of CYPs, particularly CYP3A4 and other drug-metabolizing enzymes, in cancer medication resistance will be covered in the current review.One of the biggest obstacles to the treatment of diseases, particularly serious conditions like cancer, is therapeutic resistance. The process of drug resistance is influenced by a number of important variables, including MDR genes, drug efflux, low-quality medications, inadequate dosage, etc. Drug resistance must be addressed, and new combinations based on the pharmacokinetics/pharmacodynamics (PK-PD) characteristics of the partner pharmaceuticals must be developed in order to extend the half-lives of already available medications. The primary mechanism of drug elimination is hepatic biotransformation of medicines by cytochrome P450 (CYP) enzymes; of these CYPs, CYP3A4 makes up 30–40% of all known cytochromes that metabolize medications. Induction or inhibition of CYP3A4-mediated metabolism affects the pharmacokinetics of most anticancer drugs, but these details are not fully understood and highlighted because of the complexity of tumor microenvironments and various influencing patient related factors. The involvement of CYPs, particularly CYP3A4 and other drug-metabolizing enzymes, in cancer medication resistance will be covered in the current review.

Cite this article as:

Pandey Kumar Swaroop*, Verma Sona, Upreti Shobha, Mishra Anuja, Yadav Neha and Dwivedi-Agnihotri Hemlata*, Role of Cytochrome P450 3A4 in Cancer Drug Resistance: Challenges and Opportunities, Current Drug Metabolism 2024; 25 (4) . https://dx.doi.org/10.2174/0113892002312369240703102215