Oncology Frontier: How do the molecular differences of colorectal cancer subtypes affect treatment response to targeted therapy and/or chemotherapy?

　　《肿瘤瞭望》：结直肠癌的分子差异如何影响了靶向治疗和化疗效果？

　　Dr Tejpar: That is an interesting question for two reasons. Firstly， when you look at these intrinsic biological subtypes， they differ quite strongly in biology so you would expect that not all drugs would work homogeneously across all subtypes. That is a no-brainer. When we annotate the biological differences between these groups， it becomes obvious that some of the favored pathways we tend to use as drug targets are differently expressed between patients. So we can clearly offer up the hypothesis that there is not going to be homogeneity in terms of efficacy of response. The second point relates to managing expectations and encouraging people to do work on this topic. If you really want to prove it unquestionably and have true clinical impacts， we need a lot of studies to do that. This is what we are doing now. We are taking defined subgroups and applying them retrospectively to a lot of drug trials. We look at how drug efficacy rates according to these groups. Then the next step is to do the same thing prospectively by trying to find fault with the hypothesis by using control groups to determine the differences. I want to rally the community around the enormous amount of work that needs to be done. For four or five different trials， we need to reanalyze outcomes， plus several prospective trials need to be done. I have no doubt that any type of biological subclassification of any cancer will impact drug response， clinical care and patient management but it is going to take a big community effort to get there and all stakeholders need to be involved. That means we need to go back through the academic trials， we need to reanalyze pharma research and we need to get the momentum up for new trials that incorporate some level of stratification to at least make things easier afterwards. That means a whole system needs to be functioning.

　　Tejpar博士：结直肠癌在生物学上差异巨大，其对常用靶向治疗的反应也不同。我们正在把患者进行分子分型，进行不同的药物试验，检测不同药物的疗效，并进行对照研究。我毫不怀疑结直肠癌生物亚型可影响药物治疗反应、临床护理、患者的管理，但是还需要大量临床研究验证。