Role of pharmacogenetics for the improvement of cancer treatment

• Main Authors: Vita Dolžan, Petra Bohanec-Grabar, Cristina Rodriguez-Antona
• Format: Article
• Language: English
• Published: Slovenian Medical Association 2007-12-01
• Series: Zdravniški Vestnik
• Subjects: cancer treatment; genetic variability; pharmacogenetics
• Online Access: http://vestnik.szd.si/index.php/ZdravVest/article/view/1981

<p><strong>Background:</strong> Cancer chemotherapy is associated with a great heterogeneity in patient response that makes the prediction of tumor response and/or drug toxicity very difficult. Many factors such as tumor biology, patient’s age, sex and organ function, are known to affect the therapeutic effects of drugs. Although these factors may be considered in decisions on the treatment regimens, the same regimen may result in undertreatment and insufficient therapeutic efficacy in some patients, while it can lead to overtreatment and increased toxicity in other patients. There is increasing evidence that genetic variability in drug metabolizing enzymes and/or drug targets influences drug response and may have a great impact on treatment outcome. This may be especially important for drugs with a narrow therapetic window and high level of toxicity, such as anticancer drugs. Many studies have shown that genetic variation of drug metabolizing enzymes such as cytochromes P450 (CYPs), UDP-glucuronosyltransferase (UGT), glutathione transferases (GSTs), thiopurine methyltransferase (TPMT) or dihydropyrimidine dehydrogenase (DPYD), drug transporters such as p-glycoprotein (MDR1) or reduced folate carrier (RFC1) and drug targets such as thymidylate syntahse (TYMS) or 5,10-methylenetetrahydrofolate reductase (MTHFR) influence not only the pharmacokinetics and/or pharmacodynamics of anticancer drugs but also the outcome of cancer treatment. In addition, somatic variations in the cancer cells can also have an impact on the anti-cancer drug efficacy, such as epidermal growth factor receptor 2 protein (HER2) overexpression and epidermal growth factor receptor (EGFR) mutations.</p><p><strong>Conclusions:</strong> By studying the genetic variability of drug response, pharmacogenetics offers the possibility to identify patients that could benefit most from a particular treatment as well as those at increased risk for severe toxicity thus holding promises for a more individualized cancer treatment.</p>