Laurent-Puig Pierre, Lièvre Astrid, Ducreux Michel, Loriot Marie-Anne
Université Paris-Descartes, Inserm UMR-S U775 Bases moléculaires de la réponse aux xénobiotiques, Hôpital Européen Georges-Pompidou, Pôle de biologie, Pôle de cancérologie.
Bull Cancer. 2008 Oct;95(10):935-42. doi: 10.1684/bdc.2008.0728.
Several drugs have been developed and demonstrated similar efficacy in colorectal cancer treatment therefore with choice, time comes for decision. The biologist will have to provide the tools allowing to clarify this choice. Among the tools available, those of pharmacogenetics and pharmacogenomics appear most promising and recent examples allow to illustrate their clinical interest. The pharmacogenetics of anti-cancer agents presents a clinical characteristic, which requires to hold into account the genetic variations not only of host cells but also of those of the tumor cells. Among the most conclusive examples one is that of the prediction of severe neutropenia induced by the irinotecan among patients homozygous for * 28 allele of UGT1A1 enzyme which conjugates SN38 active compound of irinotecan, the other one is the presence of a KRAS mutated allele in tumor cell to predict resistance to anti EGFR antibodies in the treatment of colorectal metastatic cancer.
已经研发出几种药物，并且在结直肠癌治疗中显示出相似的疗效，因此到了做出选择的时候了。生物学家将必须提供有助于明确这种选择的工具。在现有的工具中，药物遗传学和药物基因组学的工具似乎最有前景，最近的实例可以说明它们的临床价值。抗癌药物的药物遗传学呈现出一种临床特征，这不仅需要考虑宿主细胞的基因变异，还需要考虑肿瘤细胞的基因变异。最具说服力的例子之一是，对于UGT1A1酶*28等位基因纯合的患者，伊立替康诱导的严重中性粒细胞减少症的预测，UGT1A1酶可结合伊立替康的活性化合物SN38；另一个例子是肿瘤细胞中存在KRAS突变等位基因，以预测在结直肠癌转移癌治疗中对抗表皮生长因子受体（EGFR）抗体的耐药性。
