Personalized Cancer Therapy Considering Cytochrome P450 Variability
Abstract
The individual variability of pharmacokinetics is underestimated and few systematic studies exist in this field. In most cases, this leads to unwanted side effects or toxicity. In polychemotherapy, prodrugs (like ifosfamide), which have to be activated by cytochrome P450 enzymes (CYPs), play an important role. If patients are poor metabolizers for these drugs, the therapy will be ineffective. Furthermore, CYPs and transporters can be (over)expressed in target tissues, which is also not examined and considered in clinical routine. Here, we present a body map showing relevant enzymes in some organs and tissues. Finally, a typical case of a Caucasian chemotherapy patient with breast cancer is presented and discussed regarding a personalized cancer therapy considering the single nucleotide polymorphisms found via genotyping.
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CYP3A4 carries out the detoxification of several major anticancer medications in the clinic, such as docetaxel, irinotecan, gefitinib, cisplatin, paclitaxel, tamoxifen, and vinorelbine.
“The detoxification of several major anticancer medications in the clinic, such as docetaxel, irinotecan, gefitinib, cisplatin, paclitaxel, tamoxifen, and vinorelbine, is carried out by CYP3A4.28,29”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [29]
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Marzi, M., Ghasemian, A., Ghanbariasad, A., Nournia, E., & Zarenezhad, E. (2026) · RSC Advances · doi:10.1039/d5ra09799a
- Authors
- Preissner, S., Simmaco, M., Gentile, G., & Preissner, R.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Azienda Ospedaliera Sant'Andrea (IT)
- Venue
- Advances in Pharmacology
- Publisher
- Elsevier
- Published
- 2015
- Volume
- 74
- Pages
- 113-130
- ISSN
- 1054-3589 (ISSN-L)
- OpenAlex
- W843437442
- Cited by
- 12
- References
- 0
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2018: 1 · 2017: 1
- FWCI
- 3.85
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Advances in pharmacology (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- precision oncology, cytochrome P450, pharmacokinetic variability, prodrug activation, ifosfamide, poor metabolizers, drug toxicity, tissue-specific enzyme expression, drug transporters, single nucleotide polymorphisms, breast cancer chemotherapy, pharmacogenetics
- MeSH terms
- Cytochrome P-450 Enzyme System, Genotype, Humans, Neoplasms, Prodrugs, Polymorphism, Single Nucleotide, Precision Medicine
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