大家好，我的名字叫John Heymach Hi, I'm John Heymach,
是MD安德森癌症中心的头颈胸肿瘤科的临床主任 I'm the chairman of thoracic, head and neck medical oncology at MD Anderson Cancer Center.
很高兴今天能为《抗癌卫士》介绍一些肺癌知识 I am to be speaking on behalf of Anti-cancer Guard.
首先我要进行一下历史回顾 I'll give you a little historical perspective.
在过去，我们MD安德森使用的是PCR检测技术 We used to just test for one or two genes at a time,
所以，每次只能测1-2个癌症基因 so initially we were using PCR-based assays.
到今天，这个技术仍然在很多地方被使用 PCR-based assays are still in use in a number of places.
我们这边也用过一段时间其他检测方法，比如Sequenom 等等 There were other tests like Sequenom that we used for a period of time,
但现在，MD安德森癌症中心基本都在用NGS检测 but right now what we're using at MD Anderson, and what's really taking over in a lot of areas,
是一种叫做“新一代基因检测” is what we call Next-Gen-Sequencing, or NGS.
那“新一代基因检测”能做什么呢 What Next-Gen-sequencing does,
它不仅仅可以让医生知道自己感兴趣的基因，比如EGFR或ALK is let you not only look at your gene of interest, for example, EGFR or ALK,
还能够同时看一大片的基因位点 but simultaneously look at a whole range of genes.
当前在MD安德森，通常一次性能够完成50个基因的测序 We are commonly looking at 50 genes at once at MD Anderson,
接下去将会拓展到一层次检测200个基因位点 and this is rapidly expanding up to a panel of 200 genes.
这个技术很重要，因为它不仅仅让医生看到某一个基因 This is important, because it lets us not only look at the one gene of interest,
还可以同时看到其他的信息，比如肿瘤药物抵抗基因 but look at a number of different resistance mechanisms,
甚至在部分患者中，发现一些我们没有意识到的突变 or detect genes that we didn't even realize were mutated, that may be activated for a given patient.
当前，还有一项技术也令我十分激动 The newest method that's emerging that I think is very exciting,
它靠血液就能检测出基因突变 is looking in the plasma for detecting mutations.
当前有几个公司拥有这个技术 There's several new technologies.
一个是罗氏公司的，另一个是Guardant 公司 One of them is from Roche Diagnostics, there's another one from Guardant.
还有许许多多的公司也正在研发这种血液基因检测的技术 There's a whole host of other companies that are developing plasma-based assays.
虽然血液检测的准确性没有肿瘤检测那么好 These plasma-based assays are, while they're not quite as good yet as the tumor for looking at mutations,
但是它非常方便 they're dramatically easier.
这是该技术能够普及的立足点 I think these are gaining a foothold and becoming very popular.
特别是EGFR T790M突变，用血液基因检测特别有效 The plasma-based assays are particularly useful for detecting EGFR T790M mutations.
另外，它不仅能在治疗初期能检测，而且在治疗过程中的任何一个时间点，都能再做 The reason it's useful there, is because these don't emerge necessarily in the beginning of treatment, they can emerge at any time.
避免了医生及患者一次又一次的重复做穿刺基因检测 This can prevent you from having to biopsy a patient over and over to look for them.
只要抽血就能检测 You can run a plasma test.
因此，现在我们的典型的方法，就是在治疗的初期，先做穿刺进行NGS多位点测序 What we would typically do then, is do a biopsy in the initial staging, do next-generation sequencing in the beginning.
然后，当肿瘤开始出现药物抵抗的时候，进行血液基因检测肿瘤突变 Then, as the tumor begins to develop resistance, that's where we may use the plasma-based assays,
避免患者受到重复的穿刺痛苦 to save the patient from having to undergo repeat biopsies.
不幸的是，目前我们还没有药物去治疗每一种单基因“驱动突变” Unfortunately, right now we don't have drugs to target every single driver mutation.
介绍一下什么叫驱动突变 Just to review what a driver mutation is,
例如在肺癌中，一些时候人体的某个致癌基因启动，驱动着肺癌的发生和发展 we consider that in lung cancer, there's sometimes our single oncogenes, that when they're turned on, really drive the tumor.
这些致癌基因中，最有特点和最为人所熟知的，就是EGFR基因 The first and the best characterized one, was EGFR,
只要抑制了EGFR基因，就能控制住70-80%的肺癌患者疾病发展 and we know that blocking EGFR can be dramatically effective in 70% or 80% of patients at least.
另一个很常见的肺癌致癌基因叫K-Ras基因 The most common driver oncogene for lung cancer is K-Ras.
K-Ras大约出现在25%的肺腺癌中 K-Ras is in about 25% of lung adenocarcinoma.
目前，我们还没有通过FDA认可的方法来治疗K-Ras基因突变型肺癌 Right now, we don't have approved therapies for K-Ras mutant lung cancer.
但MD安德森有几个非常有前景的研究线索 We have several promising leads, MEK inhibitors are one of those,
其中之一叫做MEK抑制剂，目前美国还没有通过允许使用这个药物来治疗K-Ras突变型肺癌 but there are none of them that are yet approved in the United States, at least for treating these patients.
近期我们MD安德森癌症中心公布了一个有趣的研究结果 One of the interesting thing's that's emerged recently,
我们发现了一整簇新的之前从没有发现的驱动致癌基因 is we've discovered a whole host of new driver oncogenes that we didn't even realize that were there before.
其中，有一些非常罕见，比如RET融合，ROS1融合 Some of these are rare, like RET fusions, ROS1 fusions.
有一些常见于其他类型的肿瘤 Some of them occur in other tumor types,
例如BRAF突变在肺癌中只有1%或2%的发病率，但在黑色素瘤中的发生率高达60% like BRAF mutations that are present in 1% or 2% of lung cancer, but are present in 60% of BRAF mutant melanoma.
但令人欣慰的是，虽然这种突变在肺癌中出现的几率非常低 The wonderful thing here is even though they're rare in lung cancer,
但我们可以学习到其在黑色素瘤中所表现出来的特性，并使用同样的药物来治疗 we can learn from everything that's been done in melanoma, and use a lot of the same drugs.
例如，在美国我们正在尝试使用达拉菲尼，或维罗非尼或达拉菲尼/曲美替尼组合 For example, in the United States, we'll test drugs like Dabrafenib, and Vemurafenib,
这几种药物看起来可能对控制肺癌有很好的效果 or combinations like Dabrafenib and Trametinib look like they may be very effective in lung cancer,
因为它们已在黑色素瘤中被广泛使用 the same way that they've proven to be effective in melanoma.
一些致癌基因，例如肺癌中常见的EGFR以及K-Ras突变 For driver oncogenes, we have some that are common in lung cancer like EGFR and KRAS,
有药物能治疗它们，另外一些致癌基因则目前没有药物 we have drugs for some of those, not for others.
在肺癌中，还有许多罕见的致癌基因，我们正在从这些基因在其他肿瘤中的表现来学习借鉴 Then we have a lot of rare oncogene drivers where we can learn from what's happened in other tumor types,
并把其应用到肺癌的治疗中 and take the lessons from the other tumor types and apply them in lung cancer.
治疗方法的关键就是研究致癌基因 It really depends on the oncogene.
这也是近几年非常有意思的研究之一 This is one of the things that are interesting.
用专业术语来说，就是有些时候肿瘤“沉溺于”一些特定的致癌基因 The term we use sometimes is that the tumors may be addicted to a given driver oncogene.
其中，有一部分肿瘤有更强的“成瘾性” There are some tumors that appear to be more addicted than others to their oncogene,
我们还没有发现是什么原因导致这种不同的“成瘾性” and we don't understand why this is different.
我们以EGFR突变来举例，如果是Exon21突变型(L858R)的话 If you take the example of an EGFR with a sensitizing mutation, like an L858R or an Exon 19 deletion,
我们非常有信心治疗会起到效果 in those cases we can be very confident the patients can respond.
大约80%的该类型的肿瘤，会对EGFR抑制剂产生比较强的反应 About 80% of the time they're going to have a major response,
剩下那20%部分人即使效果不明显，但至少也有弱反应 and even in the patients who don't have a major response, they have at least a minor response to treatment.
所以通常来说，EGFR突变的肿瘤对这条代谢通路非常“依赖成瘾” Usually, EGFR mutant tumors are very addicted to that pathway.
而另一种致癌基因，K-Ras突变型肺癌，则只有10-20%的肺癌对MEK抑制剂有效 In the case of KRAS mutant lung cancer, only 10% or 20% may respond to a MEK inhibitor.
那这种肿瘤的成瘾依赖性就小很多 There, there is much less addiction to that particular driver.
再举个例子，例如ALK突变，它就和EGFR突变比较像，有效率可以达到70-80% In the case of others like ALK, it's more like EGFRs, 70% or 80%.
另外还有一些致癌基因，我们刚开始研究 We have some that we're just starting to target right now.
比如最近我们刚启动对RET融合型肺癌的研究 Recently we've started a study for RET fusion lung cancer.
早期临床试验结果显示，RET融合型肺癌对药物治疗是有反应的 For RET fusion lung cancers, the early data suggest that it's going to be responsive,
但并不如EGFR突变型来的那么显著 but not quite the way EGFR mutant tumors are.
大约只有一半的人的治疗反应比较好 Perhaps half of the patients will respond to good RET inhibitors,
但药物效果的持续时间也不如EGFR型来的长 but the responses aren't lasting as long as they do for EGFR.
因此在我们肺癌研究者面前的一个任务，就是搞清楚为什么有的肿瘤对致癌基因成瘾，而另一些则不成瘾 The task in front of us lung cancer researchers is to figure out why some tumors are more addicted than others,
并研究出更好的治疗方法 and figure out better therapies.
当肿瘤产生药物抵抗的时候，找出为什么它们会产生药物抵抗 When the tumors become resistant, figure out why the tumors are becoming resistant,
然后改变治疗策略来应对它 and develop strategies for targeting them.
所以这是一个很重要的问题，如何挑选合适的治疗方案 I think it's a great question of how do we sort out what the right therapy is.
这就形成了一个很有趣的现象，针对某一个特定的代谢途径，就有许多的不同的药物 This becomes particularly interesting when we've got a lot of drugs now that target one pathway.
还是以EGFR作为例子，在美国，我们有靶向药物埃罗替尼和阿法替尼 If you take EGFR as an example, in the United States, we have Erlotinib and Afatinib.
在世界上多数的其他国家，有吉非替尼还有埃克替尼可以使用 In most of the rest of the world you also have Gefitinib. We have other drugs out there like Icotinib,
我认为很快，第三代靶向抑制剂就能上市，可以针对某一个突变位点进行特异性抑制 and we very soon, we expect we will have the third-generation inhibitors, the mutation-specific inhibitors,
这样我们就有更多的用药选择 that we're going to be able to use more broadly.
像这样的第三代靶向抑制剂目前就有AZD9291 、CO-1686 、Ruxolitinib等 These are drugs like AZD9291 or CO-1686 or Ruxolitinib, as examples.
我们有那么多种药物可以选择，那么哪种效果最好呢？ We've got all these choices, how do we pick which one is best?
这真的需要一段时间才能解决这个问题 This is really going to take the field a while to sort out.
在一些案例中，我们可以根据药物毒性做出选择 In some cases, we can do it based on toxicity.
例如，第一代的靶向抑制剂不仅对EGFR突变的肿瘤有效果 For example, the first-generation inhibitors inhibit not only the mutant EGFR,
对EGFR野生型的肿瘤，也有一定的疗效 but also the wild-type EGFR.
但对于EGFR野生型的肿瘤患者来说 When you inhibit the wild-type EGFR,
其药物毒性作用会比较严重，因为药物把正常组织的EGFR受体一起抑制了 you get all the toxicities that happen from inhibiting EGFR in normal tissues.
这些不良反应包括皮肤的皮疹痤疮、消化道腹泻 This includes rash, like acne, it includes diarrhea from inhibiting it in the GI tract,
间质性肺炎等等 it includes things like interstitial pneumonitis in the lung.
而如果是第三代EGFR靶向抑制剂，就完全不同了 The third-generation inhibitors have a very different profile,
它们几乎没有这一类的副作用 where they don't have nearly as much of those toxicities.
从这方面来讲，它们更加优秀 In that way, they may look superior.
我们知道，即使是某一特定基因的突变，也可以分成许多不同类型 We also know that there are differences in the specific mutations,
例如，T790M二级突变，我们则有药物来应对 so we have some drugs, for example, that inhibit the T790M secondary mutation.
还有另外一些药，则对点缺失或者点突变的基因来的更有效，例如L858R突变 We have other drugs that look like they may be a little bit better against deletions or the point mutations like L858R.
目前在肺癌研究领域，最大的挑战是 One of the big challenges in the field,
我们对一些常见的突变有很好的应对方法 I think we have a very good sense of the common mutations,
例如之前提到过的L858R，Exon21突变型 again the L858Rs, the Exon 19 deletions, and some of the resistance mutations,
但那些罕见的突变，则还基本未知 but what about these rare mutations?
通过大量的临床研究，我们知道到了大量的肺癌罕见突变 From doing large clinical studies, we're learning about a whole host of rare mutations
但我们仍然缺乏足够临床数据 that we don't have a lot of data about.
例如，在过去的两周内，我这边收治了4位Exon20插入突变型肺癌患者 In the past two weeks, for example, I've had four patients that have Exon 20 insertions.
这种肺癌对第一代靶向治疗药，埃罗替尼和吉非替尼的反应很差 These are not very responsive to first-generation inhibitors like Erlotinib and Gefitinib.
我们怎么给这些患者治疗呢？ What are we going to use for these patients?
我们只能尝试第三代靶向治疗药物，但目前还不知道结果如何 Well, we're hopeful about third-generation inhibitors, but we don't know yet.
我们目前正在归纳整理这些病例 We're just starting to develop information from this.
因为它们非常稀有 Because these are fairly rare,
而第三代EGFR抑制剂还没有经过时间的验证，我们也不知道所有的治疗结果 and the new EGFR inhibitors haven't been tested for very long, we don't know the answer to all this.
我们只有把它们的数据放在一起，通过不断收集临床数据 To put this together, what we really need is more clinical data to tell us when you've got,
不仅是常见突变，更要收集罕见突变的数据 not the common mutations, but the rare mutations.
我们该如何选择最合适的药物？ How do we match the right drug?
我们是否能在一开始就预测出某一个药物的毒性反应呢？ When you take a look at the toxicity, can we start to predict who would benefit from a given drug?
这也是肿瘤研究过程中很有趣的一点 The reason I think this is interesting,
有的患者会出现严重的皮肤毒性表现 is we sometimes have patients that have horrible skin toxicity.
而有的患者，则完全没有皮肤毒性表现 Other patients who have nothing at all in terms of skin toxicity.
我们目前还不知道，为什么不同的患者，对药物毒性反应会有如此显著的不同 We don't understand yet why some patients get these toxicities, some who don't.
不同种族的人群，对药物的毒性反应也完全不同 There are some ethnic differences in toxicities between the drugs.
例如，大量的临床数据表明，亚洲人比高加索人或者白种人 For example, from large studies, we had seen that the rates of interstitial pneumonitis in the lung
有着更高的概率罹患间质性肺炎 seem to be much higher in Asians than in Caucasians or the western populations.
我们不知道这种药物反应差异是如何产生的 We don't understand why these differences happen,
但确实不同种族的人群对治疗的耐受度不同 but there are certainly ethnic differences,
这也能帮助我们来选择合适的药物 and these can help inform our choices of drug as well.
我认为，当前在肺癌治疗方面我们有许多药物可以选择 I think what's happening now in the field, is for the first time, we have a lot of different choices.
一般来说，有选择总是好的 Choices are generally good,
但医生要基于很多信息才能做出选择 but with choices, you need to start then getting more detailed information.
比如，考虑到了药物的毒性作用了么？ How do you choose on the basis of toxicity?
如何给予个性化的治疗？ How do you personalize therapy?
患者种族考虑到了吗？ Do you use ethnicity as a factor?
考虑了患者的性别了吗？ Do you use gender, male versus females?
是否检测了所有的突变位点来决定使用哪种药物了么？ Do you use the specific mutations like T790M, Exon20
检查了T790M突变、Exon20突变和其他罕见突变了吗？ and all these other rare mutations that happen, to help you choose?
目前仍然有许许多多的工作放在我们面前 There's a lot more work in front of us,
但好的一面是，至少我们比以前有了更多的方法可供选择 but the good news is now we have a lot more choices than we did before,
现在的药物比以往的更有效 the drugs are more effective than they ever were before,
患者也因为有了更多的治疗方法而受益 and so now patients benefit from us having these choices.
当前，在美国，我们有两种治疗方法通过了FDA允许 Right now, in the United States, we have two choices that are FDA approved.
埃罗替尼和阿法替尼是FDA允许的一线用药 Erlotinib and Afatinib are FDA approved as first-line therapy.
而第三代靶向抑制剂还正处在临床试验中，但数据显示有很好的效果 We expect, based on the great data that we've seen from the third-generation inhibitors,
我真心希望在不久的将来，第三代靶向抑制剂例如AZD9291或CO-1686等等可以通过FDA批准 that in the future we'll have the choice for the third-gen inhibitors like AZD9291 or the CO-1686,
成为备选的药物之一 if they do get FDA approved.
初期的实验结果显示比较乐观，但目前实验还未结束 The early data is promising, but they're not approved yet.
因此目前第三代靶向药物还不在选择范围内 We don't have those choices yet.
我们只能选择埃罗替尼或者阿法替尼 Right now, we choose between Erlotinib and Afatinib.
吉非替尼过去也是一个备选，目前在世界其他国家还能使用 Gefitinib also used to be an option, it's an option in the rest of the world.
该如何在这几种药物中选择呢？ Howe do you choose between them?
需要考虑以下几点，首先是药物的毒性 There's a couple of considerations. There's the toxicity profile.
吉非替尼的毒性作用最低 Right now, Gefitinib has the most favorable toxicity profile.
对于EGFR患者来说，吉非替尼、埃罗替尼、阿法替尼三个药物的毒性效果差的不大 For EGFR mutants today that look similar between Gifitinib and Erlotinib. Afatinib has a similar profile.
目前还没有直接的临床试验，来面对面比较这三个药物在EGFR突变型肺癌中的作用 These drugs haven't been compared head-to-head in EGFR mutant lung cancer,
但有一个最新的临床试验叫LUX-Lung 8 but recently there was a study called LUX-Lung 8.
这个LUX-Lung 8 实验第一次显示出来 LUX-Lung 8 directly compared, for the first time,
阿法替尼作为第一代靶向药物，其治疗效果要好于埃罗替尼 Afatinib, with a first generation inhibitor, Erlotinib. Afatinib was superior.
这个研究比较的是鳞状细胞肺癌，这类肺癌通常没有EGFR突变 That was in squamous cell cancer which doesn't usually have EGFR mutations.
他们通常是野生型EGFR They usually have wild-type EGFR,
但这是第一个3期临床随机对比实验，面对面的比较几个不同的EGFR抑制剂的治疗效果 but it was the first time EGFR inhibitors were compared head-to-head like that in a randomized phase 3 trial.
现在，有了这个实验数据，我们知道在大群体中，阿法替尼的效果可能更加好一点 Now we've got data for that population that tells us that Afatinib may be a little bit better.
对于EGFR突变型肺癌，目前还没有临床证据证明哪个药物更好 For EGFR mutants we don't have that data yet,
我们只能选择毒性小一点的药物 so we're still using toxicity to help us select.
就我个人来说，我一般通常选择将阿法替尼作为首先用药 Personally, what I do is, I'll often start with Afatinib,
因为只有它是被FDA允许，可以作为一线用药使用在EGFR突变的非鳞状细泡肺癌 because it's only approved for first-line non-squamous histology with EGFR mutants.
埃罗替尼我会作为二线药物使用 Erlotinib I can also use later,
或者将埃罗替尼和阿法替尼联合使用 or I can use Erlotinib in combinations that aren't yet available with Afatinib.
如果你的患者是EGFR突变或是ALK突变型肺癌 If you've got a patient that has an EGFR or an ALK mutation,
是否可以以常规化疗作为初始用药呢？ do you start with chemotherapy?
还是以靶向药物作为初始用药？ Do you start with a targeted agent?
这里面要分成很多条路来讨论 There's a couple of different ways to make the decision.
我告诉你我实际诊疗中是怎么处理的 I'll tell you the one practical issue that happens.
有的时候，患者确诊肺癌过来找我，他们需要立即接受治疗 Sometimes when a patient comes in, they need to start treatment quickly,
但基因突变检测往往需要一些时间才能出结果，可能要数周 and sometimes the mutation data takes a little while to come back. It may take a few weeks.
所以，我在不知道肿瘤基因突变情况下，一般会先给予化疗 So sometimes we start with chemotherapy because we don't know if they're going to have a mutation.
我会先开始治疗，然后等报告回来 Once we've started treatment, the data comes back.
那种情况下，报告回来的时候，患者一般已经完成了一个疗程四个周期的化疗 In that situation, I will typically complete a full course of chemotherapy, all four cycles,
那时候，我会再给予EGFR抑制剂来维持治疗效果 and then I'll start the EGFR inhibitors in the maintenance setting.
这就是我在不知道基因信息的时候给予的治疗方案 That's if I don't know before I start treatment.
当然，最理想的状态，是治疗前我就能知道肿瘤基因突变信息 Ideally, we'd like to know before we start treatment.
这时候我就能和EGFR突变型肺癌患者解释病情，讨论用药 If I do know before a patient starts treatment, I discuss the options with the patient,
并以EGFR抑制剂作为初始用药，而不是使用化疗药物了 but usually we start with an EGFR inhibitor if they have an EGFR mutation.
这里面有非常重要的一点，到目前为止，临床试验数据显示 I think it's important to point out that the clinical data, so far,
以化疗药作为初始用药，和以EGFR抑制剂作为初始用药，其患者的总生存率是没有显著差异的 says there's no difference in overall survival, whether you start with chemotherapy or an EGFR inhibitor.
但EGFR抑制剂作为初始用药的情况下，无进展生存期、控制肿瘤生长方面，会显著优于一般化疗药物 Progression-free survival, how long it takes the tumor to grow, is significantly better when you start with the EGFR inhibitor.
毒性反应方面，也是EGFR抑制剂明显小于化疗，患者耐受度会好很多 Toxicity is certainly better with an EGFR inhibitor. It's much better tolerated than chemotherapy.
我的经验法则就是 My rule of thumb is to
给予患者我手上最好的治疗方法 take the best treatment I have in my hand,
给患者选择毒性最小的治疗方法 and the least toxic treatment I have in my hand,
尽我所能，尽量延长最好的治疗方法使用期限 and use that best treatment first, and use it for as long as I can.
因此，我也倾向于将EGFR抑制剂作为初始用药 Part of the reason I also prefer to start with an EGFR inhibitor,
如果将来新的EGFR抑制剂上市后，我会选择使用新一代的药物作为初始用药 is we have so many new EGFR inhibitors coming down the road, that I may start with a first-generation inhibitor.
当肿瘤出现药物抵抗的时候 Then, if the tumors become resistant,
我们会考虑给予第三代靶向药物进行治疗 we often have clinical studies with third-generation inhibitors then.
我们会将患者纳入到临床试验中，给予第三代靶向药物并观察疗效 We can move to a third-generation inhibitor in the setting of a clinical trial,
希望在不久的将来，这个药物能被FDA批准，这样更多的患者能够用到 and hopefully in the near future, these will become available options if they are FDA approved.
有必要指出的是，对于EGFR突变型肺癌患者来说，常规化疗仍然是一个非常有效的治疗方法 It is worth pointing out that chemotherapy is still an effective option for people with EGFR mutations.
有的患者可能不是很知晓 Sometimes, there's some confusion about this point.
认为对于EGFR突变型肺癌，化疗的效果不好 There is an idea that chemotherapy doesn't work well in patients with EGFR mutations.
但实际情况是，EGFR抑制剂可以作为初始用药 The truth is, an EGFR inhibitor may be a better starting drug,
但后期，使用常规化疗，也能对EGFR突变肿瘤起到很好的治疗效果 but chemotherapy works very well for patients with EGFR mutations.
如果患者有EGFR突变的情况下，其化疗的治疗效果，是远好于没有EGFR突变的肿瘤的 In fact, if you have an EGFR mutation, you're more likely to respond to chemotherapy, than if you don't have an EGFR mutation.
有EGFR突变的患者，其EGFR抑制剂和化疗的治疗效果往往会更好 People with EGFR mutations respond better to both EGFR inhibitors and to chemotherapy,
这也导致了，有EGFR突变的患者，其生存周期会更长，治疗会更有效 and this helps account why they have a much longer lifespan and more effective therapies.
这也引出了更进一步的问题 One other interesting question that's raised here.
我们知道对这类患者，EGFR抑制剂有效，化疗有效 We know that EGFR inhibitors work, we know that chemotherapy works.
我们可以把两者结合一起使用，来增进治疗效果吗？ Can we bring those together to make even more effective therapies?
临床试验显示，如果把EGFR抑制剂和化疗药物一起使用 Interestingly, when you combine EGFR inhibitors and chemotherapy together,
其效果并不比单一用药来的好 they don't work any better than either one alone.
你可能会想，一个药物很有效，另一个药物也非常有效 You might think that if one works well, the other works better,
两个药物结合在一起用，理论上应该更加有效 you put them together they'll work even better.
但实际上，除了特定情况外，我是不会把这两个药物联合使用的 I don't actually combine the two, but what I will do sometimes,
这个特定情况就是，在化疗初期，我会使用一些EGFR抑制剂来控制肿瘤 is start with the chemotherapy, and then use an EGFR inhibitor as maintenance therapy to keep it down,
或者当肿瘤出现一些药物抵抗的时候，会添加使用化疗药物 or, if the tumor becomes resistant, then use chemotherapy.
这背后的科学依据是，我们认为，对EGFR抑制剂有抗性的细胞，仍旧可能对化疗产生反应 The scientific rationale behind that is we think that the cells that may be resistant to EGFR inhibitors, may still be responsive to chemotherapy,
所以我认为考虑这两种不同的治疗选项是很重要的 so that's why I think it's important to go in between those two different options.
我们很兴奋的看到免疫疗法最终也成为了有效可行的治疗选项 Finally, we're very excited about the possibilities of immunotherapy getting worked into this landscape as well.
在过去的一年内，我们第一次能够使用纳武单抗(Nivolumab)作为治疗选项 For the first time this past year, we have options like Nivolumab available.
纳武单抗是FDA唯一批准通过的治疗鳞状细胞癌的抗PD-1靶向药物 Nivolumab is only FDA approved for squamous cell cancer right now,
但是最近的ASCO会议中有数据显示，这个药物在非鳞状细胞组织学中也有效 but we have data that from this recent ASCO meeting, that it looks like it's effective in non-squamous histology as well.
现在，对于EGFR突变的患者来说，不仅仅只有两种治疗选项 Now instead of just thinking about two options for people with EGFR mutations,
即EGFR抑制剂和化疗，现在有了第三种选项 EGFR inhibitors and chemotherapy, now there's a third factor.
那么免疫疗法到底怎么样？我们如何将其结合进来？ What about immunotherapy and how do we combine that?
我们认为这些将在未来的几年内成为非常令人兴奋的话题 That's a story we think is going to become very exciting over the next couple of years.
如何将EGFR抑制剂，免疫疗法和化疗组合起来得到最好的治疗效果？ How do you combine EGFR inhibitors, immunotherapy and chemotherapy to come up with optimal treatments for patients?
我认为对于EGFR突变的患者来说，一个重要的问题就是 I think this is an important issue for people with EGFR mutations is,
我们有了第三代药物，为什么我们仍旧在使用第一代药物呢？ we've got third-generation drugs, why are we still using the first-generation ones in there?
首先，让我来简单的说明一下第一代和第三代EGFR抑制剂之间的差别 First, let me talk just briefly about the differences between first-generation and third-generation EGFR inhibitors.
第一代EGFR抑制剂，像吉非替尼和埃罗替尼，最初是开发用来抑制野生型EGFR The first-generation EGFR inhibitors, drugs like Gifitinib and Erlotinib, were initially developed to inhibit the wild-type EGFR,
之后被发现也可以抑制突变型EGFR and it was later discovered that they also inhibited the mutated EGFR.
第三代则是专门开发用来抑制EGFR突变的，所以对于野生型EGFR几乎没有作用 The third-generation was developed specifically for EGFR mutations, so they had very little activity against wild-type EGFR.
所以，第三代药物有的毒性作用往往更小 As a result, they have a much better toxicity profile.
它们会引起更少的皮疹，痤疮，胃肠道毒性例如腹泻，更少的间质性肺炎，所以它们的毒性更小 They have much less of the rash, the acne, the GI toxicity like diarrhea, less of the interstitial pneumonitis, so they have a better toxicity profile.
对于EGFR突变的患者，第三代药物很有可能会更加有效 For EGFR mutated patients, they're probably going to be more active as well.
更重要的是，它们对T790M耐药突变有效，而这类突变第一代药物是无效的 Most importantly, they inhibit the T790M resistance mutation, which is not inhibited by the first-generation.
这就是第一代和第三代药物的区别 That's the differences between the first and the third-generation.
现在，第三代药物被放在第一代药物后进行使用，能够表现出非常好的效果 Right now, the third-generation drugs have established wonderful activity when they're used after first-generation,
尤其是对于那些T790M继发突变的患者 specifically in patients with T790M secondary mutations.
我预计，如果第三代药物通过了FDA审批，它们的临床使用范围 I would expect that that's going to be the first application clinically if they do become FDA approved,
将是被用在第一代药物之后作为二线用药，尤其是对于继发T790M突变的患者 is going to be to use after a first-generation drug, specifically for people with T790M secondary mutation.
那么将它们用于一线初始治疗会怎么样呢？ What about using them in the first-line setting?
现在看来，第三代药物如果被用于一线治疗，在任何方面和第一代相比，并不会有更好的效果 It looks like they're going to be every bit as active, if not more active, than the first-generation drugs if you use them in the first-line setting.
我认为这将成为一个主要的研究领域 This is going to become, I think, a major area of development.
目前已有数个相关的临床试验正在进行中，我们安德森癌症中心也有一些研究 There's already clinical studies going, and we have several of them going at MD Anderson right now,
用来直接比较第一代和第三代药物，看谁更有效 comparing first-generation and third-generation drugs head-to-head to see which is more effective.
现在，如果你比较吉非替尼，埃克替你和埃罗替尼，我们并没有很多数据能够区分它们 Right now, if you compare Gefitinib, Icotinib and Erlotinib, we don't have a lot of data that separates those.
这三种药物都很有效 It looks like all three of those are effective drugs.
所有这些药物都能够治疗EGFR突变，而毒性特征则非常相似 All of them can work against patients with EGFR mutations, and toxicity profile is relatively similar between them.
在毒性方面只有一些微小的区别，但是它们都是非常有效的药物 There are some subtle differences in toxicity, but all of them are active and effective drugs.
而这些药物都不能够对继发T790M突变型肿瘤产生作用 None of them are going to be highly active against the T790M secondary mutation, is what we'd predict.
而我将说的是，有部分数据显示，阿法替尼这种已经在美国和欧洲通过FDA批准的药物 I'll mention that there is some data, for example, suggesting that Afatinib, which is approved in the United States and Europe and other parts of the country,
可能在某种程度上能够对继发T790M突变有作用，尤其是当和西妥替单抗一起使用时 may be somewhat active against the T790M secondary, particularly if it's combined with Cetuximab.
已经有研究证实，这两种药物的组合能对T790M突变有效，但是这种药物组合还没有获得FDA审核 There's been clinical studies that support that the two-drug combination might be effective against T790M, but it isn't yet FDA approved, that two-drug combination.
现在，这三种在中国获得批准上市的药物，之间的区别是较小的 Right now, between the three drugs that are approved in China, the differences between them are relatively modest,
选择使用哪个药物，主要方法也是根据毒性大小来选择 and it's just slight differences in toxicity would be the main way to select between them.
它们的作用机理方面没有本质上的区别 There's not major differences in their spectrum of activity.
我认为当第三代药物可以使用时，那么在选择药物方面就要更加的谨慎 I think it's when the third-generation drugs become available, that one's going to have to be much more careful in selecting,
并确保使用了正确的药物 and make sure you've got the right drug there.
很重要的问题就是，我们是否应该根据药物皮疹来指导用药 It's a great question as to whether we should be using rash to guide us.
回溯过去，当这些药物在90年代和2000年初被测试的时候 To go back, when these drugs were first being tested in the late '90s and early 2000s,
我们经常能看到患者有得了这种痤疮皮疹，而且这种皮疹的严重程度似乎和疗效有关联 the toxicity everybody saw was this acne rash, and there seemed to be some association between a severe rash and the benefit.
那时我们还没有得到初始数据，还不知道患者是否有EGFR突变 This was before we knew patients had EGFR mutations, when this initial data emerged.
那时候，皮疹的严重程度是药物使用量的一个标准，患者所用的药物的总量，一般越高，则皮疹就越多 Rash is often a marker of the drug exposure, the total dosage that you get, so higher doses of the drug are associated with more rash.
举例来说，吉非替尼，500mg每天的用量就比250mg的有更多的皮疹 For example, for Gefitinib, the dose of 500 mg a day had much more rash then the 250 mg.
现在我们知道是因为有EGFR突变的存在，这类突变患者的治疗效果令人激动 Now that we know that there is EGFR mutations and those are the patients who are getting the most dramatic benefit,
所以，现在对于治疗EGFR突变型患者，皮疹已不再是重要的标志 it appears for patients with EGFR mutation, rash is not an important marker.
弄清楚，患者的肿瘤是哪种类型突变是非常重要的 It's much more important which mutation you have in your tumor.
野生型EGFR的患者，EGFR抑制剂能够有一些效果，虽然没有EGFR突变型患者获得的那么多 For patients with wild-type EGFR, the EGFR inhibitors do have some benefit, although not as much as in the patients with EGFR mutation.
对于野生型EGFR的患者，我们认为哪个药物的疗效更好，皮疹可能是一个更加准确的参考物 For those patients, the patients with wild-type EGFR, we think that rash may be a more accurate marker of who's going to benefit,
因为皮疹能够显示出哪个药物的使用剂量更高 because there it's really telling you who got a higher dose.
如果我们回溯过去的研究，在野生型EGFR患者中，剂量才看起来有重要的影响 If you look back at the early studies, it looks like it was really in the patients with wild-type EGFR, where the dose make more of a difference.
如果患者有EGFR突变，则其突变才是影响谁能够获利的因素，不是剂量，也不是皮疹 If you've got an EGFR mutation there, it's the mutation that predicts who's going to benefit, and not the dose, and not the rash.
我认为，化疗的发展速度没有像靶向治疗和免疫疗法等领域那样发展的这么迅速 I think the progress in chemotherapy has not been nearly as rapid as it has in areas like targeted therapies and immunotherapy.
对于非鳞状细胞型肺癌，现在美国的标准疗法是培美曲塞和铂化物 Right now the standard in the United States for non-squamous histology, would be Pemetrexed and platinum.
卡铂和紫杉醇的是另一种公认的标准疗法，不管用或不用贝伐单抗 Carboplatin and Paclitaxel would be another acceptable standard with or without Bevacizumab,
我会说，化疗在这些年的进展是不大的 and I'd say the progress here has been pretty modest in recent years.
主要的进展是用什么靶向药物和化疗进行组合使用 The main progress has been what you combine with the chemotherapy.
在美国，贝伐单抗是一个通过FDA批准，可以和化疗进行组合的药物 In the United States, Bevacizumab is one approved agent to combine with chemotherapy.
现在，在安德森癌症中心，我们关注的是 For us right now, at MD Anderson, the most exciting questions we're asking is,
“如何将免疫疗法与化疗结合起来？” "How do we combine immunotherapy with chemotherapy?"
化疗药物方面，近几年只有很少的进展 In terms of looking at different chemotherapy agents, a little bit less progress.
最近几年出现的新药是Abraxane（紫杉醇蛋白质结合颗粒注射悬液）和Nab-Paclitaxel（白蛋白结合型紫杉醇） One new drug that's emerged in recent years, is Abraxane or Nab-Paclitaxel.
这是一种新的紫杉醇，通过与某一类的蛋白集合，使得药物能够更好的到达肿瘤组织 This is a version of Paclitaxel chemotherapy that's conjugated to a type of albumen that makes it a little better delivered.
Nab-Paclitaxel和Abraxane有许多优势 Nab-Paclitaxel or Abraxane has several advantages.
患者较少出现传统紫杉醇时候那样的过敏反应，因为可以避免使用溶解紫杉醇所需的毒性溶剂 One is you don't have the same allergic reactions that you do to regular Paclitaxel because you don't have to give it with the same toxic vehicle that we have to give Paclitaxel with.
紫杉醇的可溶性很差，我们需要使用一种称为克列莫佛的溶剂来溶解 Because Paclitaxel is poorly soluble, we have to give it with something called the Cremophor vehicle.
患者出现的身体毒性反应，就是因为这种溶剂所引起的，而不是化疗或者过敏反应 Very often the toxicity people have, is because of that vehicle, not because of the chemotherapy and the allergic reactions.
Nab-Paclitaxel的过敏反应很少，是其优势 Nab-Paclitaxel has that advantage in terms of fewer allergic reactions.
Nab-Paclitaxel的优势同时还有脱发少，较少出现周围神经病变和骨髓抑制 Nab-Paclitaxel also has some benefits in terms of less hair loss, a little different neuropathy profile, and a little less bone marrow suppression.
而它的药效，则与传统的紫杉醇差不多 In terms of activity, it appears to be comparable with regular Paclitaxel,
并且对鳞状细胞性肺癌细胞更加有效 with the one subgroup of squamous cell being a group where it seems to have greater efficacy.
一项由Mark Socinski和他的同事们进行的研究表明，在鳞状细胞肺癌中 A study by Mark Socinski and colleagues showed that in squamous histology,
肿瘤细胞有更高的药物反应率，对Nab-Paclitaxel和卡铂的反应也比对传统紫杉醇和卡铂的反应要大得多 patients seemed to have greater response rate, greater major responses to Nab-Paclitaxel with Carboplatin than they did to just old Paclitaxel with Carboplatin.
我认为Nab-Paclitaxel在美国也有在使用 I think Nab-Paclitaxel is used somewhat in the United States.
我不会说这是标准治疗流程，但是人们确实在使用这种药物 I wouldn't say it's a standard, but it's a drug that people do use now,
这也是在过去几年内关于化疗发生的一个重要的进步 and that would be one advance that's happened in the last several years with chemotherapy.
我认为基因测序技术将是一个非常令人兴奋的领域，它将改变我们治疗肺癌的理念 I think differences in DNA sequencing technology, I think are really going to be one of the most exciting areas that are going to change how we treat lung cancer patients.
请让我来仔细的阐述一下 Let me describe that in a little more detail.
几年前，我们只有两个基因组是用于肺癌标准检测的，EGFR和ALK Up until the last couple years, we really had two genes that were part of the standard testing for lung cancer, EGFR and ALK.
只有这两个基因组是能够影响治疗策略的 Those were the only two genes that could impact the treatment.
如果患者有EGFR突变，则接受EGFR抑制剂 If you had an EGFR mutation, you get an EGFR inhibitor.
如果患者有ALK融合基因，则接受ALK抑制剂，例如克唑替尼 If you had an ALK fusion, you'd get an ALK inhibitor like Crizotinib.
现在，情况发生了改变，因为医生可以做快速EGFR测试 Now, the landscape has really changed because just as quickly as you could do an EGFR test,
用相同的成本，目前在美国可以做至少50个基因组的测序 and for the similar cost in the United States at least, you can now profile 50 genes, or more, in a lot of cases.
其结果就是，当你测序所有相关基因组的时候，就能发现之前没有发现的基因亚型 One of the consequences though, is when you profile all these genes, you start finding these rare subgroups that we never found before,
我们就必须思考如何去治疗它们 and we have to think about ways to treat them.
举例来说，现在有1%或2%的肺癌患者是BRAF突变，比如V600E To give an example, in lung cancer patients now we have BRAF mutations like V600E in about 1% or 2% of lung cancer patients.
我们以前从未发现过这类突变，因为从未检测过，但是现在通过新的测序工具，我们正在发现类似的突变 We never used to find these, because we never looked for it before, but now that we looked in these next-generation sequencing panels, we're finding mutations like this.
幸运的是，我们从黑素瘤中了解到如何去使用BRAF抑制剂进行治疗 Fortunately, we've learned from melanoma, how to treat these with BRAF inhibitors,
像达拉菲尼和维罗菲尼，或者联合使用曲美替尼之类的MEK抑制剂，我们能够学习如何去治疗它 like Dabrafenib and Vemurafenib, with or without MEK inhibitors like Trametinib, so we can learn from there how to treat it.
我们也发现新的基因融合，像RET融合，ROS1融合 We also get new rare fusions like RET fusions, ROS1 fusions,
有一大堆FGFR融合，我们甚至发现了一个非常罕见的HER2亚组突变 there's a whole host of FGFR fusions, there's FGFR mutations emerging, we even have a rare subgroup with HER2 mutations.
HER2是乳腺癌中常见的基因 HER2 amplification is common in, and well-appreciated, in breast cancer,
但直到新一代的基因测序被广泛使用前，我们并没有很好的理解HER2突变 but we hadn't really appreciated HER2 mutations until we started this next generation sequencing.
我们现在正在试图寻找对于这1%或2%的肺癌患者的最好的治疗方法 We're now in the course of trying to figure out what's the best treatment for this group that's 1% or 2% of lung cancer.
如果你问“你需要针对1%或2%的患者开发治疗方法么？” If you're saying, "Do you need to develop therapies for 1% or 2% of lung cancer?"
需要记住的是，肺癌是非常常见的一种癌症，1%或2%的肺癌患者数量就和很多其他疾病的总人数相当了 Keep in mind that lung cancer is so common, that 1% or 2% of lung cancer, is the size of a lot of other major diseases.
在美国，每年有18万人患肺癌，大约15万到16万人是非鳞状细胞细胞癌 In the United States there's about 180,000 people that get lung cancer every year, about 150,000 to 160,000 get non-squamous histology,
所以1%到2%就相当于每年有2000到3000名患者 so 1% or 2% of that could be 2,000 or 3,000 patients.
2000或3000名患者的人数已经和一些白血病人数相同了 2,000 or 3,000 patients is the size of some major leukemia subtypes, for example.
我认为没有人会争论是否要为白血病进行新疗法的进行研究 I don't think anybody would argue that that isn't important to develop new types of treatment for leukemia.
另一个让肺癌成为公众健康威胁的一个原因，是其高得病率，以及致死率 What makes lung cancer such a major problem now, is how prevalent it is, what a big killer it is.
如果我们从全球来看，甚至是肺癌的一个小小的亚型，也是一个很重大的健康问题 Even thee small subgroups of lung cancer can be major problems when you look at a global level.
在过去几年内，肺癌领域最最令人兴奋的研究进展是 This is one of the most exciting developments that's happened in the last few years,
针对那些没有突变激活的肺癌患者的治疗方法变革 is what do we do for the patients who don't have an activating mutation,
对于那些没有EGFR、ALK、RET、ROS或其他的基因突变的肺癌患者来说 who don't have EGFR or ALK or RET or ROS or one of these other targeted genes?
最新刚在美国通过FDA审核的第一个免疫疗法药物，纳武单抗完全改变了现状 What's happened in the United States recently that's really changed the landscape, is the FDA approval of Nivolumab as the first immunotherapy drug that's approved,
我们期望还有更多的药物通过审批上市 and we expect there will be a lot more coming.
在安德森癌症中心，我们当前有超过30个针对肺癌和头颈部癌的不同免疫疗法组合的临床试验在进行 At MD Anderson right now, we have more than 30 trials of different immunotherapy combinations happening in lung and the head/neck groups,
我们正在尽快研究如何将这些免疫疗法药物进行结合使用，或者和其他疗法进行联合使用 so we're really quickly learning how to combine these immunotherapy drugs with each other, or with new types of treatment.
如果是以前，如果患者没有EGFR突变，我们会说“你只能接受化疗” It used to be the case, that if you didn't have an EGFR mutation we said, "All you've got is chemotherapy,"
然后我们并不对效果抱有太大的希望 and we didn't hold that much hope for a lot of benefit.
现在情况不同了，那些没有基因突变的肺癌患者，对免疫疗法的反应很好 What's exciting, is that it looks like a lot of the patients who don't have a targetable mutation, seem to be very responsive to immunotherapy.
举例来说，鳞状细胞肺癌，我们通常没有有效的靶向药物 As an example, squamous cell histology, where we don't have targeted drugs that are effective yet,
但他们对免疫疗法的效果比较好 seems to be the group that's most responsive to immunotherapy.
另一个好的方面是，免疫疗法他的效果可以持续很久，经常可以持续很多年 The other things that's exciting, is that patients who respond to immunotherapy, often have very durable benefit that can last for years and years.
对于我自己的鳞状肺癌病人，之前没有太多的治疗方法，现在我已经用了几年的免疫治疗 Now I've got patients in my clinic with squamous histology, where before we had very few options that we've been treating for years with these drugs.
有趣的是，往往那些重度烟瘾患者，以及对靶向治疗反应最差的患者，他们是对免疫疗法反应最好的一群人 Interestingly, it's patients who are heavier smokers, and those are the ones who respond least well to targeted agents, who seem to be the most responsive to immunotherapy.
这正填补了之前靶向疗法无法满足的患者需求 It's really filling a need for patients that was unmet before by targeted therapies.
这为之前没有很好的治疗方法的患者打开了一个全新世界的大门 It's opened a whole new world for a lot of patients before that didn't have good treatment options.
现在，肺癌领域里最激烈的问题就是，如何预测不同的肺癌患者，对免疫疗法的效果？ Right now, this is one of the burning questions in the field of lung cancer, is how do you predict who's going to respond to different types of immunotherapy?
现在我们没有确切的答案 Right now, we don't have any firm answers.
我们可以预见其将比驱动突变来得更加复杂 We can see it's going to be more complicated than for driver mutations.
如果患者有EGFR突变，则对EGFR抑制剂就肯定有反应 If you've got an EGFR mutation, you respond to an EGFR inhibitor.
在这里，我们的研究对象是人体免疫系统，我们试图增强人体的免疫系统，情况更加复杂 Here, you're targeting the immune system and trying to amp up the immune system, and so it's much more complicated.
去年有关于纳武单抗的临床试验结果公布 The data that's come out in the last year from the studies with Nivolumab,
我们如何判断谁能够从免疫疗法中获得收益？ one of the really burning questions in the field right now, is how do we predict who's going to benefit from immunotherapy?
我们知道这远比靶向药物更加复杂 We know that this is going to be a more complicated question than for targeted agents.
对于靶向药物是否有效，是十分直接了当的 For targeted agents, it can be pretty straightforward.
如果患者有EGFR突变，则接受EGFR抑制剂治疗 If you've got an EGFR mutation, you get an EGFR inhibitor.
有ALK融合，则接受ALK抑制剂 An ALK fusion, you get an ALK inhibitor,
但是对于免疫疗法来说，我们没有一个简单的标志物去测试 but for immunotherapy, we don't have a simple marker to test.
在最近大量研究中，其中有一个叫做Checkmate-017号研究，现在已经有了057号研究 From the recent large studies that have been reported, one of them is call the Checkmate -017 study, now there's Checkmate -057.
这些是专门研究纳武单抗的 These are the studies with Nivolumab.
另一个叫KIN001研究，是研究Pembrolizumab（一种PD-L1单抗MK-3475）的 The other is the KIN001 study. This is with Pembrolizumab, another PD-1 inhibitor.
通过这几项研究，我们可以看到的是PD-1或PD-L1与免疫疗法疗效之间是有一定联系的，但是从各方面来看尚不是很完美 We can see there's some association between tumor PD-1 or PD-L1, and likelier to responding to these drugs, but it's not perfect, by any means.
PD-1和PD-L1阴性的肿瘤对这些抑制剂也有很好的反应 There are tumors that are negative for PD-1 or PD-L1, that can respond very well to these inhibitors.
也有很多阳性的肿瘤对这些药物完全没有反应 There's tumors that make a lot of these markers that don't respond at all.
而且，当我们组合多个免疫疗法药物时，比如讲纳武单抗和伊匹单抗一起用的时候 Also, it looks like when we combine immunotherapy drugs, for example, a combination of Nivolumab and Ipilimumab.
PD-1及PD-L1就不是一个很合适的治疗标志物 We see there that tumor cell PD-1 or PD-L1 does not appear to be a good marker in that case.
所以，我们目前还不确定用哪种标志物来预测免疫疗法的效果 Finally, we're not sure how to use mutations also to help predict whether you're going to respond to immunotherapy.
更多种类的突变和对免疫疗法的反应可能有关联，但是这种关联现在还没有被建立起来 There does seem to be an association between a greater number of mutations and your likelihood of responding to immunotherapy, but this is not really well-established yet.
最后一个复杂的地方，是大家都在采用不同的检测方法 The final complication is everybody's running different tests.
许多制药公司都有自己测试PD-L1肿瘤细胞的方法 If you look at the pharmaceutical companies, each one of them has their own test for scoring tumor cell PD-L1,
没有一家使用相同的抗体，也没有一家用一样的评分体系 none of them use the same antibodies, none of them use the same scoring system.
因此现在主要的挑战就是，如何规范化的测试标准，让医生能够知道什么样的人群能够对免疫疗法产生反应 One of the challenges in the field right now, is how do we standardize the testing, and how do we predict who's going to respond to different immunotherapies.
这将是我们在未来几年内要去解决的很重要的一个问题 This is going to become an important area that we're going to have to address in the next few years.
在肺癌治疗领域，我们第一次有了很多优秀治疗方案可以选择 In lung cancer, for the first time, we have a few different great treatment options.
我们有免疫疗法，有靶向治疗，我们还有常规化疗 We've got immunotherapy, for certain patients we have targeted agents, and we've got chemotherapy.
还有一个我们不知道答案的问题就是，“我们如何结合这些疗法？” One question we don't know the answer to yet, is, "How do we best combine these?"
有人可能会说，“如果这些方法都有效，为什么不将它们全部拼凑起来？” You might say, "If these different things work, why not put them all together?"
当我们将它们拼凑起来，有时候它们互相之间会有反作用，或者互相拮抗，所以仅仅是简单的组合不能够使治疗更有效 When we put them together, sometimes they can counteract each other, or antagonize each other, and so putting them together might not be more effective.
举例来说，当我们组合靶向治疗和化疗，结果常常是没有单独使用任何一个来的有效 To give an example, when we combine targeted therapy with chemotherapy, often it was less effective than either one alone.
对于免疫疗法，我们知道化疗和放疗会杀死免疫细胞 In the case of immunotherapy, we know that chemotherapy and radiation can kill immune cells.
可以想象，如果激发了免疫系统后再用放化疗，会抵消免疫疗法的效果，消灭免疫细胞 You can imagine if you stimulate the immune system and then give radiation or chemotherapy, you might counteract the effect and wipe out some of the immune cells.
另一方面，放化疗也可能使免疫治疗获得更好的疗效 On the other hand, chemotherapy or radiation might make immunotherapy more effective.
我们用化疗杀死癌细胞，然后让免疫细胞更容易的攻击肿瘤 You can imagine if you kill cancer cells with chemotherapy, then get the immune cells attacking the tumor,
被化疗杀死并放出的肿瘤抗原能够比肿瘤没有死亡之前更好的被免疫系统识别 you're going to be releasing all these tumor antigens that the immune system might be able to better recognize, than if you hadn't killed any of the tumor ahead of time.
这些可能性都是我们正在进行临床试验所在研究的 These are possibilities we're now investigating in our clinical studies.
当前在安德森癌症中心，先放疗后免疫治疗，先化疗后免疫治疗，或者同时进行放化疗和免疫治疗，都在进行研究 Right now for the first time we're testing radiation followed by immunotherapy, or chemotherapy followed by immunotherapy, or testing them simultaneously.
我们还不知道结果会是怎么样，但这一领域正是我们在积极的探索的 We don't know the answers to this yet, but this is an area where we're actively investigating,
而且我认为，这是肿瘤科医生需要研究的一件很重要的事情 and I think this is going to be one of the big things that cancer doctors are going to have to figure out now.
我们有这些不同的试验在进行，我们应该如何把它们结合起来寻找一个治疗肺癌最好的方法呢？ We've got these different things that work, how do you put them together to create the best treatments possible for lung cancer patients?
每年在美国有18万人患肺癌，肺癌也是全球最大的致死疾病 One of the tragedies of lung cancer is that about 180,000 people in the United States every year get it, and it's the biggest killer worldwide.
很不幸的是，但是在大部分情况下，当被发现和检查出来的时候，已经太晚了，且不能够手术切除 Unfortunately, in the vast majority of cases, it's detected too late to cure it as it currently stands. It's caught too late to do surgery to remove the tumor.
这是因为当肺癌发展时，在扩散之前是没有任何症状的，所以我们经常很晚才检查出来 This is because when lung cancer develops, it often doesn't cause symptoms until it's already spread, and that's why we often detect it too late.
不像女性会经常做乳房X线检查，我们不会经常做肺癌筛查 Unlike women who get mammograms to try to detect breast cancer, we don't routinely do screening tests for lung cancer,
而当患者出现症状的时候，已经太晚了 and by the time it causes symptoms, at that point it's often too late.
最近一个叫研究简称NLST，即国家肺癌筛查试验的数据表示 Recent date from a study called the NLST, the National Lung Cancer Screening Trial,
如果肺癌高危人群，接受低剂量CT检查，是可以在早期发现疾病的 shows that if you actually screen patients with a low dose CT scan, who are at high risk for getting lung cancer, you can detect it early.
如果能够在早期发现的话，那么治愈率将超过95% If you detect it early, you can cure about 95% or more of those patients.
但是肺癌筛查也有问题，为什么我们不对每个人做筛查呢? There is a problem with lung cancer screening though, and why don't we use it for everybody?
因为筛查有很多的假阳性 The problem is that there's a lot of false positives.
也就是说，当进行筛查的时候，经常会发现很多不是癌症的结节 This means when you run the test, very often you detect nodules that aren't cancer,
所以在一些情况下，患者将经历不必要的手术所造成的不便和伤害 so in some cases you'll do a surgery and put patients through all the inconvenience and harm that a surgery may do,
但是最终却发现只是感染，也就是所说的肉芽肿，或者老年结核病，或者类似的不是癌症的疾病 and it may turn out that they just had an infection, what we call a granuloma, or old tuberculosis, or something like that, and it wasn't really lung cancer.
所以说现在最需要去做的，就是找到尽早发现肺癌的方法，必须更有效，且排除假阳性 Really, an important unmet need that the field has to address, is how do we detect lung cancer early, more effectively, get rid of the false positives?
我们努力要去做的，就是找到一种可以和CT检查配合的血液检查 What we're trying to do here, is develop a blood test that can work hand-in-hand with the CT scan,
就像男性可以通过血液PSA指标来检查前列腺癌一样 so in the same way that men with prostate cancer get a PSA test in the blood to detect prostate cancer,
我们希望我们能够找到类似的方法来检查肺癌 we're hoping that we're going to be able to develop the equivalent for lung cancer.
我最终的愿景就是希望有一种能够和CT配合的血液检查使得肺癌筛查能够更加的有效 What I ultimately envision, is putting together a CT screening with a blood test that may work more effectively.