Oncology Frontier: Could you explain a little bit more detail about the intra-tumor heterogeneity and modeling tumor progression?

　　Dr. Navin: Initially people thought that a single normal cell in the tissue， would acquire mutations and that single cell， after it gets enough mutations， would grow and clonally expand to form the tumor mass and it would outcompete any other cell types that are present， this big homogeneous mass of tumor cells. But as technologies have been developing and especially with next-generation sequencing， it’s been shown that there’s intra-tumor heterogeneity in breast cancer and many other cancer types， both spatially in different regions within the tumor and even intermixed in very specific locations. So it’s clear that this intra-tumor heterogeneity exists.

　　The big question in the field right now is why does it exist， why does one clone not outcompete all the other ones? One of the interesting theories is that perhaps tumor cells are cooperating to drive tumor growth and they might have some type of symbiotic relationship. And those studies are just forthcoming now， I would say. A large body of data shows that intra-tumor heterogeneity exists， and it’s certainly a problem， especially for diagnostics， because when you sample different regions you might get different mutations and the patient might respond better to certain mutations than other ones.

　　《肿瘤瞭望》：您能否详细解释一下肿瘤内异质性和肿瘤进展的模拟？

　　Navin博士：最初人们认为，组织中的一个正常细胞可发生突变，在累积足够的突变后，这个细胞将生长和克隆性扩增，超过存在的其他类型细胞，最终形成由大量均一肿瘤细胞形成的肿块。但是随着技术的进步，尤其是新一代测序技术的出现，人们发现在乳腺癌和许多其他类型的肿瘤中存在肿瘤内异质性的现象，不仅见于肿瘤内的不同区域，甚至混杂在非常特定的位置。因此，肿瘤内异质性的存在是非常清楚的。

　　目前该领域的重大问题是为什么会存在肿瘤内异质性，为什么一个克隆不能超过所有其他的克隆？其中一个有趣的理论是可能肿瘤细胞互相协作推动肿瘤生长，并且它们之间可能存在某种类型的共生关系。我认为，这些研究即将开始。大量数据显示，肿瘤内异质性是存在的，并且确实带来了一些麻烦，尤其是对于诊断而言。因为在不同区域取样可得到不同的突变，而患者对某种突变的反应可能要优于其他突变。