González-Vacarezza Nicolás, Alonso Isabel, Arroyo Gustavo, Martínez Jorge, De Andrés Fernando, LLerena Adrián, Estévez-Carrizo Francisco
Drug Metab Pers Ther. 2016 Jun 1;31(2):83-90. doi: 10.1515/dmpt-2015-0027.
Bevacizumab was the first molecular-targeted antiangiogenic therapy approved for the treatment of metastatic colorectal cancer. Until now, there are no predictive biomarkers available to decide the prescription of bevacizumab in patients with colorectal cancer. The purposes of this review were to provide a critical appraisal of the evidence and to identify possible predictive genetic biomarkers. A literature search was performed to identify studies that determine different levels of treatment response between patients stratified according to defined biomarkers. Interesting findings were reported between patients stratified according to rs3025039 and rs833061 polymorphisms of the gene VEGFA, with statistically and clinically significant differences for progression-free survival and overall survival. However, another study conducted in a larger sample does not confirm these previous findings, suggesting that well-designed prospective studies are still needed to achieve conclusive results. FLT1 (or VEGFR1) rs9513070 seems to be an interesting candidate as a predictive biomarker, with differences of more than 10 months in OS between different patients groups. In our opinion, possible interesting biomarker candidates for future research could be the polymorphisms rs833061 and rs3025039 of VEGF-A, rs9513070 or haplotype analysis of FLT1, rs2661280 of RGS5, rs444903 and rs6220 of EGF and Ang-2 or LDH plasma levels.
贝伐单抗是首个被批准用于治疗转移性结直肠癌的分子靶向抗血管生成疗法。到目前为止，尚无预测生物标志物可用于决定结直肠癌患者中贝伐单抗的处方。本综述的目的是对现有证据进行批判性评估，并确定可能的预测性遗传生物标志物。进行了文献检索，以识别那些确定根据特定生物标志物分层的患者之间不同治疗反应水平的研究。根据血管内皮生长因子A（VEGFA）基因的rs3025039和rs833061多态性分层的患者之间报告了有趣的发现，无进展生存期和总生存期存在统计学和临床意义上的差异。然而，另一项在更大样本中进行的研究并未证实这些先前的发现，这表明仍需要精心设计的前瞻性研究以获得确凿的结果。FLT1（或VEGFR1）rs9513070似乎是一个有吸引力的预测生物标志物候选者，不同患者组之间的总生存期差异超过10个月。我们认为，未来研究中可能有吸引力的生物标志物候选者可能是VEGF - A的rs833061和rs3025039多态性、FLT1的rs9513070或单倍型分析、RGS5的rs2661280、表皮生长因子（EGF）和血管生成素 - 2（Ang - 2）的rs444903和rs6220或乳酸脱氢酶（LDH）血浆水平。
