RESUMO
The goal of cancer pharmacogenomics is to obtain benefit from personalized approaches of cancer treatment and prevention. Recent advances in genomic research have shed light on the crucial role of genetic variants, mainly involving genes encoding drug-metabolizing enzymes, drug transporters and targets, in driving different treatment responses among individuals, in terms of therapeutic efficacy and safety. Although a considerable amount of new targeted agents have been designed based on a finely understanding of molecular alterations in cancer, a wide gap between pharmacogenomic knowledge and clinical application still persists. This review focuses on the relevance of mutational analyses in predicting individual response to antitumor therapy, in order to improve the translational impact of genetic information on clinical practice.
Assuntos
Genômica , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas , Farmacogenética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Receptores ErbB/genética , Receptores ErbB/fisiologia , Tumores do Estroma Gastrointestinal/genética , Genes ras/genética , Humanos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/uso terapêutico , Transdução de SinaisAssuntos
Glucosidases/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Instabilidade de Microssatélites , Mutação , Neoplasias Gástricas/genética , Repetições de Trinucleotídeos/genética , Alelos , Proteínas de Ligação ao Cálcio , Análise Mutacional de DNA , Frequência do Gene , Ácido Glutâmico/genética , Humanos , Polimorfismo Genético , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Homocysteinemia has been associated with oncogenic risk. This study was designed to investigate the homocysteine (Hcy) genotype/phenotype interactions together with the inflammatory and nutritional status of cancer patients. PATIENTS AND METHODS: The Hcy levels were analyzed in 47 cancer patients in association with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, folate and inflammatory markers. RESULTS: The MTHFR C677T and A1298C genotype distributions did not differ from those predicted by the Hardy-Weinberg distribution. Conversely, the Hcy levels were higher in the cancer patients (p=0.04), who were also characterized by low-grade inflammation. The Hcy levels correlated with the interleukin-6 (IL-6) (p=0.001), tumor necrosis factor-alpha (TNF-alpha) (p=0.042) and folate (p<0.0001) levels of the patients. Multivariate analysis showed that TNF-alpha (p=0.014) and folate (p=0.019) were independent predictors of elevated Hcy levels in the cancer patients. CONCLUSION: The MTHFR polymorphisms do not significantly contribute to tHcy (total Hcy) levels in cancer patients, and cancer-related inflammation may be associated with elevated tHcy levels, possibly involving a TNF-alpha mediated pathway.