事件记录
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主持人: 癌症本身就很难治疗，但是, 当癌症产生抗药性时, 它们变得几乎不可能停下来. 我的嘉宾博士. Trudy 奥利弗, a professor of oncological sciences at the University of Utah and a Huntsman Cancer Institute investigator, 提出了一种令人兴奋的方法来理解和对抗耐药性吗.
所以,博士. 奥利弗, I was at a talk of yours where you said that you have some crazy ideas for studying drug resistance in cancer. 你为什么觉得他们疯了? 你的想法有什么疯狂之处?
Dr. 特鲁迪奥利弗: 我想我应该说他们很有野心. 所以大发娱乐现在所处的时代，技术已经发展到大发娱乐可以发问的地步, 以一种非常全面的方式, 在一个给定的癌细胞中，所有被改变的基因是什么? 所以大发娱乐想, 第一次, 地址的阻力, 解决耐药性问题, 不是通过大发娱乐检验的特定假设，而是从全局上说什么是一切, what are all the changes that have occurred in a drug-resistant cancer cell and to integrate that knowledge with high through-put drug screening that temps to identify drugs that resistant cells are now sensitive to.
所以大发娱乐的方法非常全面, quite expensive and will generate a lot of data that we are going to have to sift through to sort of find the needle in the haystack.
主持人: 你是怎么想出这个主意的?
Dr. 特鲁迪奥利弗: 好吧, 如我所说, 时机的选择是正确的, 综合深度测序, 这是历史上第一次真正负担得起吗. 大发娱乐真的可以, 只要1000美元，而不是10美元,000 or $20,000甚至100美元,10万年前, we can pretty quickly and relatively affordably understand all of the genetic changes in a drug-resistant cell compared to a non-drug-resistant cell and that just wasn't possible before.
主持人: 你能解释一下耐药性是如何发生的吗? 我的意思是，肿瘤内部发生了什么使它具有这种能力?
Dr. 特鲁迪奥利弗: 好吧, 如果你想想肿瘤, 肿瘤由许多细胞组成, 成千上万的人, 数百万个细胞, 这些细胞并不都是一样的. They all have different properties and some of those cells are going to be sensitive to therapy and some of those cells are going to inherently have the capacity to avoid the drug. 所以发生的是敏感细胞死亡，抵抗细胞, 固有的抵抗力, 细胞存活并继续产生同样具有抵抗力的子细胞.
你可以想象一下, 因为癌症有进化和改变的能力, that the qualities that allow a tumor to resist therapy are selected for and the qualities that make them sensitive to therapy eventually go away. 这实际上是适者生存. 这是达尔文的进化论...
主持人: 正确的.
Dr. 特鲁迪奥利弗: 以非常迅速的规模...
主持人: 在你的体内.
Dr. 特鲁迪奥利弗: ...大发娱乐可以跟随它.
主持人: 可怕的.
Dr. 特鲁迪奥利弗: 完全. 这就是癌症难以治疗的原因.
主持人: 让大发娱乐来谈谈你正在应用这项技术治疗的癌症. 你在调查什么癌症啊?
Dr. 特鲁迪奥利弗: 小细胞肺癌. So small-cell lung cancer is the second to third most common type of lung cancer but it's really the most aggressive type of lung cancer. Ninety-five percent of patients with this disease do not survive five years and most of them really do not survive one year. 这是一种高度转移的疾病，所以它很容易传播，而且非常致命.
主持人: 但你是说，你之前告诉我治疗确实有效, 至少一开始是这样. 正确的?
Dr. 特鲁迪奥利弗: 正确的. Back in the 1970s doctors thought that this was going to be one of the next curable cancers because small-cell lung cancer responds exquisitely 好吧 to chemotherapy. Tumors really can sometimes just melt away and patients may think that they have a cure but the tumor cells are never completely gone. There may be only a few of them that are very difficult to see but they're there and they grow and divide and tumors come back and when they come back, 它们对曾经敏感的药物完全耐药了. And we really have no therapeutic options for patients with chemo-resistant small-cell lung cancer.
主持人: 这似乎是癌症研究的下一个前沿. 我的意思是，对付抗药性，这是一个可怕的问题.
Dr. 特鲁迪奥利弗: 绝对. We're getting better and better at treating diseases with frontline therapies but the problem is cancers can evolve and that's what makes them so deadly and so they almost always find a way to evolve around that first treatment. And then we really need to understand what do we do next and what can we do to delay that resistance process?
主持人: 所以解释一下你的方法.
Dr. 特鲁迪奥利弗: 所以大发娱乐的方法是非常综合的. We want to understand all of the genes and pathways that are altered in the course of drug resistance and then to identify the genes and pathways that are really responsible for driving that resistance so that we can stop them or prevent them from happening. 为了做到这一点，大发娱乐利用了深度测序技术. 大发娱乐正在对耐药癌细胞的DNA和RNA进行测序, 与非抗性对照相比.
And so this sequencing information will tell us all of the genes and pathways that are altered 在抵抗过程中. We're then integrating that knowledge with high-through-put drug screening where we subject the resistant and sensitive cells to large panels of drugs to ask, 好吧, 大发娱乐知道这些耐药细胞对很多东西都有抵抗力. 很多东西都不起作用，但现在的药物起作用了? 因为大发娱乐认为发生的变化, 在抵抗过程中, 也使细胞对其他东西敏感大发娱乐想要找到这些东西. And so we overlay what we know about the genetic changes that are happening with the drugs that are working to gain a better understanding of resistance and how to target it.
主持人: 在这个过程中你走了多远?
Dr. 特鲁迪奥利弗: We've been able to see in cell-lines that there are correlations with certain pathways being activated in the cancer cells and that we have drugs that are available for those pathways that are sensitizing the resistant cells to therapy. 现在大发娱乐想知道这种情况有多普遍? 这在大发娱乐观察的每一种不同的癌细胞系中都是独特的吗？还是这是一种共同的趋势?
下一步是将其应用到一个更生理的系统中，比如老鼠模型. So we do have mouse models of small-cell lung cancer and we're going to ask whether the particular drugs that we found in vitro, 在盘子里, 也适用于鼠标模型. 与此同时, we are collaborating to obtain human tissue to see whether in human tissue there's a correlation with activation of these pathways during drug resistance and, 如果有的话, 大发娱乐认为，这最终将导致一些药物进入临床试验.
主持人: 所以这是向个性化医疗迈出的一步?
Dr. 特鲁迪奥利弗: 这是正确的. 大发娱乐真的需要, 在未来, 当一个患有耐药性疾病的病人来时, 寻找特定通路被改变的证据. 如果它们被激活, 那么大发娱乐就知道特定的病人需要接受这种特定的药物.
主持人: 听起来是一项艰巨的任务. 我的意思是，你是独自在实验室做这个实验还是和其他小组一起做?
Dr. 特鲁迪奥利弗: So we are collaborating to obtain human tissue with Intermountain Healthcare and then we're also collaborating with other groups across the country to better understand the drug-resistant state. 例如, we have a collaborator in Texas who is helping us understand how the metabolism of cancer cells change 在抵抗过程中.
主持人: 你告诉我你有一个时间表.
Dr. 特鲁迪奥利弗: 我希望如此, 一年内, 考虑到大发娱乐已经确定了一些大发娱乐认为与之相关的途径, 我认为, 一年内, we should know whether or not this is translating to human tissue and whether or not these drugs are affective in mouse models and at that point we'd be able to submit a story for publication.
主持人: 听起来不错. 你研究癌症已经有一段时间了，对吗? 是什么激发了你对癌症的兴趣?
Dr. 特鲁迪奥利弗: 这是正确的. 我上大学的时候, 我有两个家庭成员, 大发娱乐家两边各一个, 他们都得了癌症，结果却截然相反. One was my uncle on one side of my family who had a brain tumor and he was diagnosed around Thanksgiving and had passed away by Christmas.
主持人: 哦,天啊.
Dr. 特鲁迪奥利弗: 非常迅速的疾病. 在我家族的另一边, my great-grandmother was 91 when my grandmother found a little mass on her neck and she discovered that she had lymphoma and began receiving chemotherapy and I went with her to her chemotherapy sessions and sat on the floor next to her. 这对我产生了巨大的影响, 在这个房间里, 很多人都在接受化疗, 从青少年到中年人再到我的曾祖母.
主持人: 是的.
Dr. 特鲁迪奥利弗: 她活了下来，活到了105岁.
主持人: 哇.
Dr. 特鲁迪奥利弗: 所以她真的是一个成功的故事. 这激发了我在大学学习更多癌症知识的兴趣. I had experience doing summer research programs and I particularly sought to do a summer research program in cancer in Colorado in the lab of Dr. 保罗。邦恩. 结果他是肺癌研究领域的世界领袖. 这是我第一次接触到癌症，这促使我去攻读博士学位.
主持人: 很好. 非常感谢你接受大发娱乐的采访.
Dr. 特鲁迪奥利弗: 谢谢你！.
播音员: 有趣的. 信息丰富的. 而这一切都是为了更好的健康. 大发娱乐是Scope健康科学广播.