Pharmacogenomics of taxane/platinum therapy in ovarian cancer.
OBJECTIVE
Taxane (paclitaxel or docetaxel) and platinum (cisplatin or carboplatin) chemotherapy is commonly used in the treatment of ovarian cancer. Despite an initial high response to therapy, the 5-year survival rate remains low. The identification of pharmacogenomic markers to identify patients unlikely to respond or at risk for severe toxicity will assist in the goal of individualizing ovarian cancer treatment.


METHODS
Most studies have assessed single nucleotide polymorphisms from genes involved in the pharmacokinetics and pharmacodynamics of the drugs.


RESULTS
Unfortunately, most markers identified have not been replicated in subsequent studies.


CONCLUSIONS
Other mechanisms of variability, including epigenetic control of gene expression and copy number variation, may play important roles. In addition, nongenetic influences such as concurrent medications, and physiological and environmental factors could also affect individual responses to taxane and platinum therapy.
Marsh
Sharon
S
Génome Québec and Montreal Heart Institute Pharmacogenomics Centre, 5000 rue Bélanger, Montreal, Quebec, Canada. smarsh@pgx.ca
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D014644:Genetic Variation / Q000502:physiology; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods*; D017671:Platinum Compounds / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage
D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D017671:Platinum Compounds; D043823:Taxoids