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\begin{document}

\title{Contributing factors on metabolic mechanism-based
CYP3A4-activated/deactivated anticancer drugs: implications for
individualizing chemotherapy}



\author[1]{Fengling Wang}%
\author[2]{Xue Zhang}%
\author[2]{Huiyu Lu}%
\author[1]{Xiangyun Meng}%
\author[1]{Xi Ye}%
\author[2]{Weidong Chen}%
\affil[1]{Hefei Hospital Affiliated to Anhui Medical University}%
\affil[2]{Institute of Drug Metabolism, School of Pharmaceutical Sciences, Anhui University of Chinese Medicine}%


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  \date{May 28, 2024}


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\begin{abstract}
Cytochrome P450 3A4 (CYP3A4), one of important members of the cytochrome
P450 subfamily, acts as a critical catalyst for multiple drug
metabolism. Pharmacological activities and clinical outcomes of
CYP3A4-metabolized anticancer drugs greatly depend on this enzyme
activity and expression, as it catalyzes a variety of reactions for drug
activation or inactivation. In view of the complex tumor environments as
well as various factors concerning CYP3A4 expression, function, and
regulation such as physiological factors, disease complications,
concomitant drugs, inflammation response and gene polymorphisms, the
pharmacokinetics of most anticancer drugs are influenced by the degree
of induction or inhibition CYP3A4 mediated metabolism. This
inter-individual variability, together with the narrow therapeutic index
of most anticancer drugs, therefore have important implications for
achieving the expected efficacy and minimized toxicity from cancer
chemotherapy in individuals. Goals of the review were to outline and
discuss significant underlying factors that contribute to differences in
drug metabolism in detail, including the expression, activity regulation
and genotype of CYP3A4 in tumor tissues. The purpose is to highlight the
clinically meaningful of CYP3A4 induction or inhibition for metabolic
activation/inactivation-based cancer therapy. Assessing inter-individual
variability of metabolic activity from multiple dimensions will
facilitate the development of robust pharmacokinetics modeling
approaches that may predict an individual's CYP3A4-activated/deactivated
drug metabolizing capacity and drug response, thereby selecting optimal
treatment regimens.%
\end{abstract}%



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