Resumo Toda publicação advinda de pesquisa científica exige respeito aos padrões de ética que caracterizam a adequada conduta do investigador, o que se traduz em integridade na pesquisa. Porém, há distinta modalidade de pesquisa, conhecida como “pesquisa clínica”, que vem buscando atuar de maneira íntegra visando fortalecer a base de seu agir em prol da sociedade em geral. A caracterização dos envolvidos e sua função ideal e real no cenário moderno foi o objetivo deste trabalho. A busca e descoberta de novas drogas beneficiarão toda coletividade, se as políticas de saúde pública forem eficazes, normatizando o acesso da população a essas descobertas. A integridade na pesquisa, portanto, precisa ampliar seus horizontes para abarcar também a pesquisa clínica, cujos partícipes devem ser orientados e cobrados quanto à boa prática nas diversas etapas de desenvolvimento do estudo, o que permitirá íntegra e exitosa investigação.
The treatment of chronic myeloid leukemia (CML) was revolutionized by the introduction of imatinib mesylate (IM). However, approximately 20% of patients are non-responsive and interpatient variability in response to IM is still a phenomenon lacking explanation. Single nucleotide polymorphisms (SNPs) located in genes encoding proteins involved in IM pharmacokinetics are potentially involved in the causes of this variation. In this study, we investigated the association of SNPs in the genes encoding IM metabolizing enzymes CYP3A4 (rs35599367 and rs2740574) and CYP3A5 (rs776746) and efflux transporter proteins ABCB1 (rs3213619, rs1128503, rs2032582 and rs1045642), ABCG2 (rs2231142) and ABCC4 (rs9561765) with response to treatment and with IM plasma through levels and hair concentrations. The analyzed sample was constituted of 182 CML patients on IM treatment. DNA samples were genotyped for the nine SNPs using real-time polymerase chain reaction. Hair and plasma trough IM concentrations were measured through liquid chromatography coupled to mass spectrometry methods. Clinical response was defined according to the European Leukemia Net guidelines. The number of responders to standard IM therapy was 104. A trend to a higher frequency of CYP3A4 *22 (rs35599367) allele carriers was observed among responders to IM (12.5 vs. 3.4% of non-responders, P = 0.087), although no significant differences in plasma or hair concentrations between genotypes were found. Pharmacogenetics may become a valuable approach to optimize therapy with IM in CML, but many factors still need to be clarified to make possible its application in clinical practice.
Disclosures
No relevant conflicts of interest to declare.
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