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The Role of Exosomal Biomarkers in the Monitoring of Bioactivation and Metabolite Clearance of Chemotherapeutics in Cancer Patients
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DOI：10.2174/0113892002399475260223055432.png)
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Abstract
En 中文
Bioactivation and clearance of anticancer agents are crucial factors in the efficacy and toxicity of anticancer drugs. Exosomes are membrane-bound vesicles secreted by tumor cells and the tumor microenvironment. These vesicles contain drug-metabolizing enzymes, transporters, and RNA. Exosomes can be non-invasively collected from the blood. This article has been prepared by combining the evidence of the role of exosomal cytochrome P450 isoforms, such as cytochrome P450 family 2 subfamily C member 19, cytochrome P450 family 2 subfamily D member 6, and cytochrome P450 family 3 subfamily A member 5, in the oxidation of anticancer drugs in the first phase of drug metabolism. Exosomal UDP-glucuronosyltransferase 1A1 has been found to help in the conjugation of anticancer drugs in the second phase of drug metabolism. Exosomal ATP-binding cassette transporters, P-glycoprotein, multidrug resistance-associated protein 1, and breast cancer resistance protein have been found to act as intercellular conveyors of drug efflux capacity. These transporters can modulate the efficacy of chemotherapy. Exosomal microRNAs, such as microRNA-21, microRNA-155, and microRNA-1246, have been found to modulate apoptosis, DNA repair, metabolic adaptation, and chemotherapy resistance through the PI3K/AKT pathway, EZH2/STAT3 pathway, and PDCD4 pathway. Long non-coding RNAs, such as UCA1 and HOXA antisense RNA, can reprogram the chromatin structure. These long non-coding RNAs can suppress tumor suppressor genes, thus leading to chemotherapy resistance. Bioinformatics pipelines have been designed to bridge the gap between exosomal RNA and protein levels in the profile of dynamic metabolic states. The challenges in the field of exosomal therapy drug monitoring have been discussed in the article. The article has recommended the use of artificial intelligence in the integration of omics with microfluidic technology for the improvement of exosomal therapy drug monitoring.
Keywords:
Exosomal biomarkers
chemotherapy resistance
drug metabolism
extracellular vesicles
bioactivation and clearance
MicroRNA
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