A simple new blood test that can catch cancer earlyJimmy Lin is developing technologies to catch cancer months to years before current methods. He shares a breakthrough technique that looks for small signals of cancer's presence via a simple blood test, detecting the recurrence of some forms of the disease 100 days earlier than traditional methods. It could be a ray of hope in a fight where early detection makes all the difference.
1,516,498 views April 2017~~July 2022 | Jimmy Lin • TEDJimmy Lin
Geneticist
TED Fellow Jimmy Lin is developing technologies to catch cancer early.
Cancer. Many of us have lost family, friends or loved ones to this horrible disease. I know there are some of you in the audience who are cancer survivors, or who are fighting cancer at this moment. My heart goes out to you. While this word often conjures up emotions of sadness and anger and fear, I bring you good news from the front lines of cancer research. The fact is, we are starting to win the war on cancer. In fact, we lie at the intersection of the three of the most exciting developments within cancer research.
00:35
The first is cancer genomics. The genome is a composition of all the genetic information encoded by DNA in an organism. In cancers, changes in the DNA called mutations are what drive these cancers to go out of control. Around 10 years ago, I was part of the team at Johns Hopkins that first mapped the mutations of cancers. We did this first for colorectal, breast, pancreatic and brain cancers. And since then, there have been over 90 projects in 70 countries all over the world, working to understand the genetic basis of these diseases. Today, tens of thousands of cancers are understood down to exquisite molecular detail.
01:16
The second revolution is precision medicine, also known as "personalized medicine." Instead of one-size-fits-all methods to be able to treat cancers, there is a whole new class of drugs that are able to target cancers based on their unique genetic profile. Today, there are a host of these tailor-made drugs, called targeted therapies, available to physicians even today to be able to personalize their therapy for their patients, and many others are in development.
01:43
The third exciting revolution is immunotherapy, and this is really exciting. Scientists have been able to leverage the immune system in the fight against cancer. For example, there have been ways where we find the off switches of cancer, and new drugs have been able to turn the immune system back on, to be able to fight cancer. In addition, there are ways where you can take away immune cells from the body, train them, engineer them and put them back into the body to fight cancer. Almost sounds like science fiction, doesn't it?
02:16
While I was a researcher at the National Cancer Institute, I had the privilege of working with some of the pioneers of this field and watched the development firsthand. It's been pretty amazing. Today, over 600 clinical trials are open, actively recruiting patients to explore all aspects in immunotherapy.
02:34
While these three exciting revolutions are ongoing, unfortunately, this is only the beginning, and there are still many, many challenges. Let me illustrate with a patient. Here is a patient with a skin cancer called melanoma. It's horrible; the cancer has gone everywhere. However, scientists were able to map the mutations of this cancer and give a specific treatment that targets one of the mutations. And the result is almost miraculous. Tumors almost seem to melt away. Unfortunately, this is not the end of the story. A few months later, this picture is taken. The tumor has come back. The question is: Why? The answer is tumor heterogeneity. Let me explain.
03:25
Even a cancer as small as one centimeter in diameter harbors over a hundred million different cells. While genetically similar, there are small differences in these different cancers that make them differently prone to different drugs. So even if you have a drug that's highly effective, that kills almost all the cells, there is a chance that there's a small population that's resistant to the drug. This ultimately is the population that comes back, and takes over the patient.
03:53
So then the question is: What do we do with this information? Well, the key, then, is to apply all these exciting advancements in cancer therapy earlier, as soon as we can, before these resistance clones emerge. The key to cancer and curing cancer is early detection. And we intuitively know this. Finding cancer early results in better outcomes, and the numbers show this as well. For example, in ovarian cancer, if you detect cancer in stage four, only 17 percent of the women survive at five years. However, if you are able to detect this cancer as early as stage one, over 92 percent of women will survive. But the sad fact is, only 15 percent of women are detected at stage one, whereas the vast majority, 70 percent, are detected in stages three and four.
04:45
We desperately need better detection mechanisms for cancers. The current best ways to screen cancer fall into one of three categories. First is medical procedures, which is like colonoscopy for colon cancer. Second is protein biomarkers, like PSA for prostate cancer. Or third, imaging techniques, such as mammography for breast cancer. Medical procedures are the gold standard; however, they are highly invasive and require a large infrastructure to implement. Protein markers, while effective in some populations, are not very specific in some circumstances, resulting in high numbers of false positives, which then results in unnecessary work-ups and unnecessary procedures. Imaging methods, while useful in some populations, expose patients to harmful radiation. In addition, it is not applicable to all patients. For example, mammography has problems in women with dense breasts.
05:47
So what we need is a method that is noninvasive, that is light in infrastructure, that is highly specific, that also does not have false positives, does not use any radiation and is applicable to large populations. Even more importantly, we need a method to be able to detect cancers before they're 100 million cells in size. Does such a technology exist? Well, I wouldn't be up here giving a talk if it didn't.
06:14
I'm excited to tell you about this latest technology we've developed. Central to our technology is a simple blood test. The blood circulatory system, while seemingly mundane, is essential for you to survive, providing oxygen and nutrients to your cells, and removing waste and carbon dioxide. Here's a key biological insight: Cancer cells grow and die faster than normal cells, and when they die, DNA is shed into the blood system. Since we know the signatures of these cancer cells from all the different cancer genome sequencing projects, we can look for those signals in the blood to be able to detect these cancers early. So instead of waiting for cancers to be large enough to cause symptoms, or for them to be dense enough to show up on imaging, or for them to be prominent enough for you to be able to visualize on medical procedures, we can start looking for cancers while they are relatively pretty small, by looking for these small amounts of DNA in the blood.
07:15
So let me tell you how we do this. First, like I said, we start off with a simple blood test -- no radiation, no complicated equipment -- a simple blood test. Then the blood is shipped to us, and what we do is extract the DNA out of it. While your body is mostly healthy cells, most of the DNA that's detected will be from healthy cells. However, there will be a small amount, less than one percent, that comes from the cancer cells. Then we use molecular biology methods to be able to enrich this DNA for areas of the genome which are known to be associated with cancer, based on the information from the cancer genomics projects. We're able to then put this DNA into DNA-sequencing machines and are able to digitize the DNA into A's, C's, T's and G's and have this final readout. Ultimately, we have information of billions of letters that output from this run. We then apply statistical and computational methods to be able to find the small signal that's present, indicative of the small amount of cancer DNA in the blood.
08:25
So does this actually work in patients? Well, because there's no way of really predicting right now which patients will get cancer, we use the next best population: cancers in remission; specifically, lung cancer. The sad fact is, even with the best drugs that we have today, most lung cancers come back. The key, then, is to see whether we're able to detect these recurrences of cancers earlier than with standard methods.
08:53
We just finished a major trial with Professor Charles Swanton at University College London, examining this. Let me walk you through an example of one patient. Here's an example of one patient who undergoes surgery at time point zero, and then undergoes chemotherapy. Then the patient is under remission. He is monitored using clinical exams and imaging methods. Around day 450, unfortunately, the cancer comes back. The question is: Are we able to catch this earlier? During this whole time, we've been collecting blood serially to be able to measure the amount of ctDNA in the blood. So at the initial time point, as expected, there's a high level of cancer DNA in the blood. However, this goes away to zero in subsequent time points and remains negligible after subsequent points. However, around day 340, we see the rise of cancer DNA in the blood, and eventually, it goes up higher for days 400 and 450.
10:01
Here's the key, if you've missed it: At day 340, we see the rise in the cancer DNA in the blood. That means we are catching this cancer over a hundred days earlier than traditional methods. This is a hundred days earlier where we can give therapies, a hundred days earlier where we can do surgical interventions, or even a hundred days less for the cancer to grow or a hundred days less for resistance to occur. For some patients, this hundred days means the matter of life and death. We're really excited about this information.
10:36
Because of this assignment, we've done additional studies now in other cancers, including breast cancer, lung cancer and ovarian cancer, and I can't wait to see how much earlier we can find these cancers.
10:52
Ultimately, I have a dream, a dream of two vials of blood, and that, in the future, as part of all of our standard physical exams, we'll have two vials of blood drawn. And from these two vials of blood we will be able to compare the DNA from all known signatures of cancer, and hopefully then detect cancers months to even years earlier. Even with the therapies we have currently, this could mean that millions of lives could be saved. And if you add on to that recent advancements in immunotherapy and targeted therapies, the end of cancer is in sight.
11:28
The next time you hear the word "cancer," I want you to add to the emotions: hope. Hold on. Cancer researchers all around the world are working feverishly to beat this disease, and tremendous progress is being made.
11:43
This is the beginning of the end. We will win the war on cancer. And to me, this is amazing news.
11:51
Thank you.
11:52
(Applause)
Mengyu Zheng, Translator
Lena Fu, Reviewer
00:01
癌症， 很多人的家人、朋友、爱人 因为这种可怕的疾病离去。 我知道观众里有一些人 是癌症的幸存者， 或者正在与病魔做斗争。 我的心和你们在一起。 人们说起癌症的时候 通常会悲伤、愤怒和恐惧， 而我今天为你们带来了 癌症研究最前沿的好消息。 事实上，我们对癌症的战争 已经开始走向胜利。 我们正面对着 癌症研究中三项最令人振奋的进展。
00:35
第一项是肿瘤基因组学。 基因组包含了 生物体中由DNA编码记载的 所有遗传信息。 在肿瘤里，DNA的变化被称为突变， 这是肿瘤失控的成因。 大约十年前，我加入了 约翰 · 霍普金斯大学的一个团队。 肿瘤突变的位置是 由他们首先绘制出来的。 我们首先完成绘制的是结直肠癌、 乳腺癌、胰腺癌和脑瘤。 从那时开始，已经有超过 90个项目在全世界 70个国家中进行， 试图理解这些疾病的遗传基础。 如今，我们对上万种癌症的理解 都已经达到了精确的分子级别。
01:16
第二项技术革命是精准医学， 也被称为“个性化医疗”。 与一刀切的癌症治疗方法相比， 有一类全新的药物可以 根据不同癌症独特的基因档案 进行针对性的治疗。 今天，有了这些被称为靶向治疗的 特制药物， 如今的医生们已经可以 为病人定制他们独有的治疗方法， 而还有更多的新疗法正在研发中。
01:43
第三项令人振奋的 技术革命是免疫疗法。 这真的很令人振奋。 科学家们试图利用免疫系统 来对抗癌症。 例如，我们已经发现了 一些遏制癌症的方法， 以及一些能够重启 免疫系统的药物 来对抗癌症。 此外，我们还可以从人体里 取出一些免疫细胞， 训练它们，改变它们的结构， 再重新放回人体内， 让它们来对付癌症。 这听起来简直像科幻小说，不是吗？
02:16
作为国家癌症中心的研究员， 我有幸与一些这个领域的先驱共事， 并在一线目睹了这些发展。 简直太不可思议了。 现在已经有超过600项临床实验 在积极招募病人来研究免疫治疗。
02:34
这三项技术革命正在进行过程中， 然而遗憾的是，这才只是开始。 我们还面临着很多很多的挑战。 让我们来看一位病人。 这位病人患上了一种皮肤癌， 叫做黑色素瘤。 这很可怕，癌症已经 遍布了全身各处。 但是科学家们得以绘制出 这种癌症的突变位置， 并对其中一种突变 进行针对性的治疗。 治疗结果几乎称得上是奇迹。 肿瘤已经几乎看不到了。 很不幸，这并不是故事的全部。 几个月后，我们拍下了这张照片。 肿瘤卷土重来了。 问题是，为什么会这样呢？ 答案是肿瘤的异质性。 让我来解释一下。
03:25
即使小到直径 只有一厘米的肿瘤 都包含了超过 一亿个不同的细胞。 尽管它们的基因很相似， 不同的肿瘤之间 还是存在微小的差异， 使得它们对不同药物 的反应不尽相同。 所以即使有一种 非常有效的药物， 能够几乎杀死 所有的肿瘤细胞， 仍然有一小部分 对药物有抗性的细胞 有机会残留下来。 最后就是这些残留的细胞 卷土重来 并遍布了病人的全身。
03:53
那么现在的问题是， 我们要怎么做呢？ 关键在于 要尽可能早地 将最新最先进的癌症治疗方法
04:03
应用在病人身上， 抢在有抗药性的癌细胞出现之前。 治疗癌症的关键在于尽早发现。 这我们一直都知道。 越早检测出癌症， 就越能更好地治疗。 这一点也在数据中有所体现。 比如说，如果患有卵巢癌的病人 在癌症四期的时候才检测出来， 只有17%的女性病人能存活五年以上。 然而，如果女性在癌症二期， 甚至一期的时候就能检测出来， 就会有超过92%的病人得以存活下来。 但令人悲痛的事实是，仅有15% 的 女性在一期癌症的时候得到确诊， 而70%的大多数病人都在 三期或四期癌症时才确诊。
04:45
我们迫切地需要更好的方法检测癌症。 现阶段最好的 癌症检测方法分为三类。 第一是医疗手段， 比如用肠镜来检测结肠癌。 第二是生物标记蛋白， 比如检测前列腺癌的前列腺特异抗原。 还有第三种是成像技术， 比如通过乳房X线照相 来检查乳腺癌。 医疗手段是黄金标准， 但是非常痛苦， 而且需要依靠大型设备来实施。 至于蛋白标记，虽然对一些人很有效， 但有些时候并不是非常准确， 造成了大量的假阳性， 并导致病人经受了多余的检查和手术。 显像技术在一些人群中很有效， 但是会让病人承受有害的辐射。 另外，并不是所有病人 都能接受显像技术。 比如说，一些女性有致密乳房， 用乳房X射线照相术检测有一定难度。
05:47
所以我们需要的是一种无创的、 仅需要小型设备、 而且特异性很强, 不会造成假阳性的方法。 这种方法还要避免辐射， 而且可以普遍用于广大病人。 更重要的是， 我们需要一种方法， 在癌症长到一亿细胞大小之前 就能检测出它的存在。 有这样一种技术存在吗？ 如果没有，我就不会 站在这里演讲了。
06:14
我很高兴能向你们介绍 我们正在研发的最新技术。 这种技术的核心是 简单的血液检验。 血液循环系统，看起来很普通， 却对我们的生存至关重要。 血液为我们的细胞 提供氧气和养分， 同时移除废物和二氧化碳。 这里有一个重要的生物知识： 癌细胞生长和死亡的速度 远超过正常细胞。 当癌细胞死亡时， 它们的DNA散落进血液里。 从各种癌症基因组测序项目中， 我们可以知道这些癌细胞的特性， 我们可以在血液中 寻找这些特殊的信号， 以提前检测出癌症的存在。 这样我们就可以不用等到 肿瘤大到已经表现出症状， 或者密度高到可以在显像中出现， 或者足够明显到 你可以通过医疗手段看到， 我们可以在肿瘤相对 还很小的时候进行检测， 在血液里寻找这些微量的DNA。
07:15
那么让我来告诉你们， 我们是如何做到的。 首先，如我所说， 我们从简单的验血开始—— 没有辐射，没有复杂的仪器—— 就是简单的验血。 然后血液样本被寄给我们， 我们会从中提取出DNA。 当你的身体基本上全是健康细胞时， 大多数检测到的DNA 都是来自健康细胞的。 不过仍然有很小一部分， 不到百分之一， 来自于癌细胞。 然后我们用分子生物技术来复制 这些与癌症基因相关的DNA， 主要根据肿瘤基因组学项目的 信息来判断是否相关。 然后，我们将这些DNA 放入DNA测序仪器， 将DNA数字化， 变成A、C、T、G组成的编码。 这就是最终的读取数据。 最终，我们会从整个过程中 得到由亿万字母组成的信息。 接下来，我们使用统计和计算方法 来寻找其中存在的微小信号， 证明血液中可能存在的肿瘤DNA。
08:25
这个方法在病人身上可行吗？ 由于目前并没有办法真的预测 哪些病人会得癌症， 我们选择了第二合适的 人群进行研究： 癌症减缓期的病人； 更具体地说，是肺癌。 令人遗憾的是，即使是 使用了现有最好的药物， 大多数肺癌还是会复发。 那么关键就在于 我们能否比标准方法更早地 检测出癌症的复发。
08:53
我们与伦敦大学学院的 查尔斯·斯旺顿教授一起探索 这种方法，并且刚刚完成了一项大型的 临床研究。 我来带你们看一个病例。 这位病人接受了手术， 这里是起始时间点。 然后他接受了化疗， 接下来他的症状开始缓解。 他一直在接受各种临床检验 和显像技术的检测。 大约第450天的时候，很不幸， 他的癌症复发了。 问题是，我们能更早地 发现癌症复发吗？ 在这期间，我们一直在 收集他的血液样本， 以便测量他血液的循环肿瘤DNA。 在开始的时候，如我们所料， 血液里的肿瘤DNA含量很高。 然而在接下来的时间点， 这些DNA慢慢消失， 一直在几乎可以忽略的水平。 在第340天前后，我们发现了 血液中肿瘤DNA水平开始上升， 最终在第400天和 第450天时上升到更高。
10:01
你也许还没意识到，这就是关键： 在第340天，我们看到了 血液里肿瘤DNA的上升。 这意味着，与传统方法相比， 我们能提前超过一百天 检测出癌症。 这说明，我们可以 提前一百天开始治疗， 提前一百天进行手术干预， 让肿瘤生长的时间减少一百天， 或者让抗药性癌细胞 少一百天的产生机会。 对于一些病人来说， 这一百天就是生与死的区别。 我们对此非常的激动。
10:36
介于这样的结果， 我们还针对其它癌症 完成了另外几项研究， 包括乳腺癌、肺癌 和卵巢癌， 我已经迫不及待地想看到 我们能多早检测到癌症。
10:52
我有一个最终的梦想， 关于两管血液的梦想， 在未来，作为我们标准体检的一部分， 我们会抽两管血。 用这两管血，我们能够比较 所有已知的肿瘤DNA， 但愿这样可以提前几个月， 甚至几年检查出癌症。 即使用我们现有的治疗方法， 这也意味着能拯救上百万的生命。 如果你再算上免疫疗法的最新进展， 以及靶向治疗， 终结癌症已经指日可待了。
11:28
下次你听到“癌症”这个词， 我希望你能感受到希望。 坚持住。 全世界肿瘤研究学者 都在狂热地工作， 想要打败这种疾病， 并且已经取得了巨大的成就。
11:43
这是终结的开始。 我们会打赢这场与癌症的战争。 对我来说，这是最棒的消息。
11:51
谢谢大家。
11:52
（掌声）
https://www.ted.com/talks/jimmy_lin_a_simple_new_blood_test_that_can_catch_cancer_early/transcript
