Molecular targets of 5FU and combined chemotherapy of 5FU plus low dose CDDP for head and neck cancer

我们对影响抗癌药物疗效的因素进行了研究，特别是5FU和CDDP，目的是为了建立能改善预后和质量的定制化化疗方案。材料和方法：1)为了保护器官，我们对头颈部肿瘤患者进行了新辅助化疗(FP)。2)采用组织培养药物反应试验(HDRA)对手术标本进行体外药敏试验，并用实时荧光定量RT-PCR方法定量检测可能调控抗癌药物的基因表达水平。结果：1)13例未经治疗的头颈部肿瘤患者接受FP治疗后，10例(77%)达到PR以上。2)随着HER-2mRNA表达水平的升高，手术标本对5FU和CDDP的抑制指数呈下降趋势，而HDRA无反应者对5FU和CDDP的HER-2mRNA表达水平呈显著上升趋势，而5FU抑制指数随COX-2mRNA表达水平的升高而上升，但其意义尚不清楚。结论：需要对5FU代谢相关因子的酶活性进行分析，并对其表达水平进行定量检测。此外，通过检测代表个体肿瘤特征的分子标志物，我们希望建立订单式癌症化疗，使我们能够通过临床试验为患者选择最佳方案。我们也希望将检测和选择基因芯片应用于分子标记。

We examined the factors regulating effectiveness of anti-cancer agents especially, 5FU and CDDP, for the purpose of establishing of order-made cancer chemotherapy that will improve prognosis and QOL.Materials and methods : 1) For organ preservation, we administered neoadjuvant 5FU and CDDP chemotherapy (FP) to head and neck cancer patients. 2) We conducted in vitro chemosensitivity tests using histoculture drug response assay (HDRA) on surgical specimens, and performed real-time RT-PCR for the quantitative detection of expression levels of mRNA that may regulate anti-cancer agents. We then analyzed the correlation between them.Results : 1) Among 13 untreated head and neck cancer patients who underwent FP therapy, 10 patients (77%) achieved PR or above. 2) Along with the elevation of HER-2 mRNA expression levels, there was a downward tendency in the inhibition index for 5FU and CDDP in surgical specimens, and we detected a significant upward tendency in HER-2 mRNA expression levels among non-responders of HDRA to 5FU and CDDP.On the other hand, the 5FU inhibition index rose with elevations in COX-2 mRNA expression levels, although the significance of this is unclear. This should be investigated in the future with a greater number of patients.Conclusion : There is a need to analyze the enzyme activity and quantitatively detect expression levels of mRNA for factors relating to metabolism of 5FU. Furthermore, detecting the molecular marker that represents the tumor characteristics in individual patients, we hope to establish order-made cancer chemotherapy that will allow us to select the best regimen for patients through clinical trials. We also hope to apply detection and selection cDNA array to the molecular marker.