[ASCO2014]BRAF抑制剂在治疗结直肠癌中的疗效评价——Alan P. Venook教授访谈

作者:  A.P.Venook   日期:2014/6/25 14:24:11  浏览量:54537

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1.为什么BRAF抑制剂在治疗BRAF突变的黑色素瘤中起作用,而在BRAF突变的结直肠癌中未见良好获益?   问题在于在不同的肿瘤中,通路是存在差异的。实际上,不同的肿瘤是通过各自不同的通路来控制疾病的行为。因此不论何种原因,在黑色素瘤中BRAF是驱动突变,并且通过控制BRAF突变可以对疾病产生很大影响。而在结直肠癌中可能是其中某一突变发挥作用,但并非主导作用。通过信息了解到,尽管在黑色素瘤中存在BRAF突变,后续应用BRAF抑制剂治疗BRAF突变已取得了效果,但是并非主要而持久的疗效。当你将BRAF抑制剂与其他的药物进行比较时,你就会有很吃惊的发现。目前的状况是大多数肿瘤不只是靠单一途径和突变介导的。胃肠道间质瘤是一个特例,c-kit突变可能被治疗并且可能在该疾病中占主导地位。所以我们不应该感到惊讶,一个通路在某一肿瘤中的行为与在其他肿瘤中是不同的。

 

  <Oncology Frontier>: The serum biomarkers, for example CA19-9 and AFP, play important roles in the early diagnosis of many kinds of cancers. Is there any new progress in the research on biomarkers in colorectal cancers? And will these biomarkers, for example sHER3, be used in clinical practice?

  《肿瘤瞭望》:血清学检测指标在许多癌症的早期诊断上起到了重要作用,如CA199,AFP等,在结直肠癌的血清学检测指标研究上有哪些新的进展?未来这些检测指标,如sHER3,是否有希望应用于临床?

 

  Dr Venook: The answer to the last question is no because it is just not ready for general use. There is a lot of interest in miRNA and circulating tumor cells and circulating tumor DNA but it is just not ready for prime time. I think the problem is that if we identify who is at risk for colon cancer (based on familial risk for example) then we can select those patients more likely to have these markers. If we take the broad population at large which includes most people who are not at risk for colon cancer, then it is like looking for a needle in a haystack. At this point, they are not ready for clinical practice but there are a lot of people looking.

  Venook博士:后一个问题的答案是否定的。目前sHER3尚未准备作为常规应用。在miRNA、循环肿瘤细胞和循环肿瘤DNA方面确实有很大的兴趣,但是目前尚未就绪。 我认为问题在于倘若我们能够确定哪些人存在结直肠癌的危险因素(比如说基于家族风险因素),我们就能更容易地筛选出可能携带这些标志物的人群。如果我们在广泛的人群中进行筛选——其中绝大部分都没有结直肠癌风险,那么就会如同大海捞针。 在这一点上,他们尚未准备好进行临床试验,但是很多人都在期待。

 

  <Oncology Frontier>: Your research of miRNA in HCC is highly regarded. Is there any miRNA in colorectal cancers that can act as a biomarker to diagnose and evaluate t reatment effectiveness?

  《肿瘤瞭望》:您以往在肝癌的miRNA研究方面获得了很好的成果,在结直肠癌中是否可能存在类似miRNA,可以作为未来结直肠癌诊断和治疗评价的指标?

 

  Dr Venook: There is actually a paper released today from a company in the US that suggests there is a miRNA that is a biomarker. This is a very complex area where even the measurement of miRNA is open to question, but it is coming into focus and we believe it may be the next frontier in terms of identifying ways of finding disease earlier.

  Venook博士:事实上,美国的一家机构今天发布一篇文章指出存在类似的miRNA生物标志物。这是一个非常复杂的领域,即使是miRNA的测定还是值得商榷的问题。但它已成为未来关注的焦点,我们相信它将会成为早期发现疾病方面的下一个前沿。

 

  <Oncology Frontier>: Anti-EGFR and anti-VEGF are two important treatments in mCRC (metastatic colorectal carcinoma). What conclusion did the CALGB/SWOG 80405 study arrive at and what is your opinion of these two therapies?

  《肿瘤瞭望》:作为转移性结直肠癌治疗的两种重要方法,抗EGFR和抗VEGF治疗效果孰优孰劣一直有着不同的争论,本次会议公布的CALGB/SWOG 80405研究结果得到了怎样的结论?您如何评价这两种治疗方法。

 

  Dr Venook: I just presented these results yesterday. It turns out that the therapies are the same. For that population of patients, essentially the outcomes are the same. We defined KRAS mutation patients as those with mutations at codon 12 and 13, and in those patients there was no difference in outcomes. The survival approached 30-months in both arms which is a real increment. The take-home message is that patients do much better than they used to although we have a lot of work to do.

  Venook博士:在本届大会上,我已提出了这些结果。研究结果证明二者疗效是相同的。对于患者,基本上结果是相同的。我们确定KRAS突变的患者存在12和13位密码子突变,且这些患者的预后没有区别。两组的生存期接近30个月,且呈正向增长。反馈的信息是患者较之前有所好转,然而我们还有很多工作需要做。

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