[Genomic markers and anticancer chemotherapy].
Worldwide research on the human genome exerts a major impact on medical science. The growing evidence that genetic polymorphisms in the metabolism, the disposition, and the targets of drugs can have an even greater influence on the efficacy and the toxicity led to the creation of a novel chemotherapeutic strategy, personalized medicine. Much effort has been directed toward identifying the indicators of individual response to drugs, and these studies have provided a variety of potent predictive markers of individual drug response, which include some significant markers in clinical practice with sufficient evidence. Personalized medicine based on the response prediction using genomic marker is increasingly being recognized as a practical treatment approach in cancer chemotherapy, and to be indispensable when molecular targeted drugs are involved in the therapy. Even so, the ingenious and intricate mechanism of individual drug response creates obstacles in predicting chemotherapeutic response: Multiple factors are involved in the mechanisms, and key factors for drug response vary significantly among individuals. DNA chip technology enables us to overview a huge number of gene expressions simultaneously, but gene expression profiles of drug sensitivity vary considerably even for the same drug, which shows the limited value of a static microarray-expression profile as a marker aimed at individualizing patient therapy. Selection of a set of truly significant genomic markers and understanding of their interplay are of key importance in prediction of individual response to drug therapies. Challenges to such biological complexity are now started to identify a better genomic marker. The contribution of genomic marker research to anticancer chemotherapy and problems of the day were reviewed.
Nishiyama
Masahiko
M
Translational Research Center, Saitama Medical University International Medical Center.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor