[SABCS2014]2014年SABCS AACR乳腺癌杰出研究奖得主——康毅滨教授访谈

作者:  康毅滨   日期:2014/12/13 17:19:02

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康教授:众所周知,癌细胞发生转移是非常棘手的问题。在循环中数以百万计的癌细胞中,仅很小一部分能最终发生转移。癌细胞转移是一种具有高度选择性的过程,只有合适的癌细胞才能发生转移。

  Oncology Frontier: Dr. Kang, thank you for joining us. You gave a presentation here, an award winning presentation on metastases, congratulations.

  《肿瘤瞭望》:非常感谢康教授接受我们的采访。首先恭喜您获奖并进行了转移癌的获奖演讲。

  Dr. Kang: Thank you.

  康教授:谢谢。

  Oncology Frontier: You talked about the heterogeneity of cells that metastasize. Could you explain that?

  《肿瘤瞭望》:您在演讲中谈到了转移细胞的异质性,请您对此作详细解释。

  Dr. Kang: So it is known that metastasis is actually a very difficult event for cancer cells. Of all of the millions of cells in circulation, only a tiny fraction is able to make metastases in the end. It is a highly selective process that only the fittest are able to make metastases.

  康教授:众所周知,癌细胞发生转移是非常棘手的问题。在循环中数以百万计的癌细胞中,仅很小一部分能最终发生转移。癌细胞转移是一种具有高度选择性的过程,只有合适的癌细胞才能发生转移。

  Oncology Frontier: How do you identify which of those cells are the fittest and target those?

  《肿瘤瞭望》:您如何从这些细胞中识别能转移的合适癌细胞进而行靶向治疗?

  Dr. Kang: We use a method called in vivo selection, basically using Darwinian selection of the fittest in vivo using a mouse as a platform. We inject human tumor cells in new mice and then follow metastases in the lung, or the bone, or in the brain. The idea is that the ones that make metastases are those fittest cells that have a specific ability to form tumors. We can then isolate sublines in all of them and we validate whether they do have increased ability to make metastases. Once you confirm that, then you have a subline with bonetropic, lungtropic, or braintropic metastatic behavior.

  康教授:我们采用了一种称为“在体选择”的方法,根据达尔文优胜劣汰法则,应用小鼠模型识别易发生转移的癌细胞。向新生小鼠体内注射人肿瘤细胞,然后观察其在肺、骨骼及脑中的转移情况。发生了转移的细胞被认为是最合适者,有形成肿瘤能力。然后从中分离亚细胞株,并进一步验证它们发生转移的能力是否增加。一旦得以证实,则获取了易向肺、骨骼及脑转移的亚细胞株。

  Oncology Frontier: Identifying those cells is one step but what is the end goal, just because you know what the cell is still want to do something about it.

  《肿瘤瞭望》:找出这些细胞只是其中一个步骤,终极目标是什么?难道只为了解到底可利用它们做些什么?

  Dr. Kang: Yes, I think in the past this was difficult. This was difficult because the in vivo approach is not new. This has been developed pioneer in the field during the 1970s. At that time we are stuck, you have the subline but you do not know what to do with it. We did not even know how many genes are in a genome, and so it is only in the last 10 to 20 years that we have genomics and polynomic studies, and now we have a quick and comprehensive view of the genome with those highly metastatic cells. On top of that, we also have clinical data from patients, so we can test which gene associates with poor outcome patients. We have both genomic advances used to increase accuracy and sensitivity in mouse models, and we also have data from clinical samples. All that combines to allow us to find the genes and validate the importance of metastases in the mouse and the clinical importance in human patients.

  康教授:找出这些细胞确实只是其中一步,但在过去这也非常困难,因为当时体内研究方法陈旧。该领域于二十世纪70年代取得了一定发展,有了亚细胞株,但当时却不知道该如何加以利用,也不知道其基因组中的基因数目。可喜的是,过去10~20年间,我们开展了很多基因组学与多态性研究,从而对具有高度特异性转移的细胞基因组有了快速而全面的认识。更重要的是还获取了患者临床数据,从而可探讨和检测哪些基因与患者预后不良相关。回顾过去,我们在基因组学方面取得了很大进步,小鼠模型研究的精确度及灵敏度得以提高,并积累了大量临床样本数据。这些均有助于我们寻找促进肿瘤转移的基因,并在小鼠模型中验证其在肿瘤转移中的重要作用,进而在人类患者中验证其临床重要性。

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