美国国家公共电台 NPR For Now, Sequencing Cancer Tumors Holds More Promise Than Proof

 

DAVID GREENE, HOST:

Cancer patients are increasingly having the DNA¹ of their tumors analyzed³ in a quest for better treatment. This is a prime example of what's known as precision medicine. That's where medical decisions are driven by data. NPR health correspondent Richard Harris reports that while there are high hopes about precision cancer treatment, the results often don't live up to the expectations.

RICHARD HARRIS, BYLINE⁴: When you hear stories about the use of DNA sequencing as part of cancer treatment, chances are they are uplifting stories, like that of Ben Stern who showed up one day in October for a follow-up appointment at the Johns Hopkins Kimmel Cancer Center in Baltimore.

BREE BYRD: We're going to the dark-blue chair. Of course, you know that.

HARRIS: Medical technician Bree Byrd settles him in gently.

BYRD: So they want to get a whole bunch more blood from you, so I have to take two today.

HARRIS: In the spring of 2016, Ben Stern was diagnosed with a deadly brain cancer, glioblastoma. He was 45 at the time. Surgeons removed what they could of the tumor². Then over the months, he got chemotherapy and radiation. He even got on a clinical trial to see if a leading edge drug called a checkpoint inhibitor would work. But he says that didn't prevent a tumor-induced seizure⁵.

BEN STERN: My whole right side clenched⁶ up, and Tara had called my 911 in the middle of it.

HARRIS: His wife Tara says another brain surgery led to yet more disappointment at a monthly follow-up appointment.

TARA STERN: The tumor had already grown back, and it was already bigger than the original sized tumor that we found the previous May. So it - you know, he took this little nugget out in March, and it grew back to this full-scale tumor that was causing more damage.

HARRIS: It did that in a month?

T. STERN: It did that in five weeks, yes.

HARRIS: Stern's doctor sent a genetic⁸ analysis of the cancer to what Hopkins calls its molecular⁹ tumor board. It's a small group of doctors who meet Mondays to review these genetic tests. They found an overactive gene⁷ that sometimes responds to a particular drug. So Ben went on it.

T. STERN: He started his next round of chemotherapy that Monday. But he didn't seem to get weaker. Like he was getting stronger kind of almost every day. It was - (laughter) it was almost miraculous¹⁰.

HARRIS: Ben says the drug even reversed his deteriorating¹¹ mental state brought on by the brain tumor. At the next monthly appointment, following a brain scan, Ben and Tara got more good news.

T. STERN: The tumor was immeasurable on that next MRI.

HARRIS: What do you mean?

T. STERN: It wasn't there, (laughter) to put it bluntly.

B. STERN: I was basically, as I am now, just in tears.

HARRIS: That gave Ben and Tara a sense that maybe they could conquer this cancer. His doctor at Hopkins, Matthias Holdhoff, was guardedly optimistic when we spoke¹² in October.

MATTHIAS HOLDOFF: We have to use these results with caution because we do not know how long this effect might wear on. But for the time being, this is a clinically very meaningful benefit.

HARRIS: It seemed like a success story in the making for precision medicine. But most stories like this don't have happy endings.

BEN PARK: We're getting better. But like many things in life, there's kind of hope and hype. And I think that that's also the reality with precision medicine right now.

HARRIS: Ben Park is an oncology professor at the Sidney Kimmel Comprehensive Cancer Center. After noticing how much confusing genetic information was flooding into doctors at Hopkins, he founded the molecular tumor board.

PARK: The reason I started this tumor board many years ago now - well, many being four - was simply because there was a patient - young woman who had metastatic breast cancer who had a mutation¹³ on one of these reports and decided¹⁴ to forego standard-of-care therapies, which have been proven to actually prolong life in this setting, and to get on a trial on a mutation that didn't really make sense. And she went on a trial. She almost died. She had real bad toxicity¹⁵ from the experimental drug.

HARRIS: She was drawn¹⁶, Park says, by the allure¹⁷ of precision medicine. The reality though is that most of the time the tests don't offer any suggestions for treatment. Only about a quarter of patients at Hopkins are steered¹⁸ toward particular drugs or toward ongoing¹⁹ clinical trials. And even that placement rate is far better than experience elsewhere. So far there's only been one randomized study to test this drug-targeting strategy. And it found no overall benefit for patients.

PARK: If you have this knowledge, it's not enough. You have to prove that acting²⁰ on that knowledge - some medical intervention²¹ will actually afford benefit for patients. That's the trickiest²², toughest part about looking at all these types of genomic tests to really prove that this is making a difference in the lives of our patients.

HARRIS: Park has since passed on leadership of the molecular tumor board to his colleague, oncologist Josh Lauring. Dr. Lauring says there are a few cancers where DNA analysis does make a clear difference - say in melanoma and certain types of lung cancer.

JOSH LAURING: In other cancers, it's really kind of an open question. At the same time, this testing is available commercially, as well as in academic medical centers, and is being done. Patients want it. Providers want it.

HARRIS: So what's happening, in effect, is a huge poorly constrained²³ experiment involving real patients treated differently in all sorts of settings. Lauring and colleagues at Hopkins are trying to keep track of all their patients - what they got, how long the treatment was successful and how long the patients lived.

LAURING: We think it's really important to capture that information as well to try to learn from it, because in many cases it's not going to be effective. But in some it is, and it's important for us to figure that out.

HARRIS: Therapies that target specific genetic patterns are appealing because medical scientists have some sense of the biology underlying²⁴ their drugs. They aren't just killing²⁵ fast growing cells as conventional chemotherapy does.

LAURING: Unfortunately in many cases, these responses - if they occur - are relatively²⁶ brief.

HARRIS: That unfortunately turned out to be the case for Ben Stern as well. Five months after his remarkable²⁷ response, Ben started feeling weaker again. An MRI suggested the cancer might be on the move, so he went back to the hospital for another round of chemotherapy and radiation. They're hoping for the best. Richard Harris, NPR News.

(SOUNDBITE OF RE:PLUS' "SUNRISE, SUNSET")

1 DNA   

(缩)deoxyribonucleic acid 脱氧核糖核酸

参考例句：

• DNA is stored in the nucleus of a cell.脱氧核糖核酸储存于细胞的细胞核里。
• Gene mutations are alterations in the DNA code.基因突变是指DNA密码的改变。

2 tumor   

n.（肿）瘤，肿块(英)tumour

参考例句：

• He was died of a malignant tumor.他死于恶性肿瘤。
• The surgeons irradiated the tumor.外科医生用X射线照射那个肿瘤。

3 analyzed   

v.分析( analyze的过去式和过去分词 )；分解；解释；对…进行心理分析

参考例句：

• The doctors analyzed the blood sample for anemia. 医生们分析了贫血的血样。 来自《简明英汉词典》
• The young man did not analyze the process of his captivation and enrapturement, for love to him was a mystery and could not be analyzed. 这年轻人没有分析自己蛊惑著迷的过程，因为对他来说，爱是个不可分析的迷。 来自《简明英汉词典》

4 byline   

n.署名；v.署名

参考例句：

• His byline was absent as well.他的署名也不见了。
• We wish to thank the author of this article which carries no byline.我们要感谢这篇文章的那位没有署名的作者。

5 seizure   

n.没收；占有；抵押

参考例句：

• The seizure of contraband is made by customs.那些走私品是被海关没收的。
• The courts ordered the seizure of all her property.法院下令查封她所有的财产。

6 clenched   

v.紧握，抓紧，咬紧( clench的过去式和过去分词 )

参考例句：

• He clenched his fists in anger. 他愤怒地攥紧了拳头。
• She clenched her hands in her lap to hide their trembling. 她攥紧双手放在腿上，以掩饰其颤抖。 来自《简明英汉词典》

7 gene   

n.遗传因子，基因

参考例句：

• A single gene may have many effects.单一基因可能具有很多种效应。
• The targeting of gene therapy has been paid close attention.其中基因治疗的靶向性是值得密切关注的问题之一。

8 genetic   

adj.遗传的，遗传学的

参考例句：

• It's very difficult to treat genetic diseases.遗传性疾病治疗起来很困难。
• Each daughter cell can receive a full complement of the genetic information.每个子细胞可以收到遗传信息的一个完全补偿物。

9 molecular   

adj.分子的；克分子的

参考例句：

• The research will provide direct insight into molecular mechanisms.这项研究将使人能够直接地了解分子的机理。
• For the pressure to become zero, molecular bombardment must cease.当压强趋近于零时，分子的碰撞就停止了。

10 miraculous   

adj.像奇迹一样的，不可思议的

参考例句：

• The wounded man made a miraculous recovery.伤员奇迹般地痊愈了。
• They won a miraculous victory over much stronger enemy.他们战胜了远比自己强大的敌人，赢得了非凡的胜利。

11 deteriorating   

恶化，变坏( deteriorate的现在分词 )

参考例句：

• The weather conditions are deteriorating. 天气变得越来越糟。
• I was well aware of the bad morale and the deteriorating factories. 我很清楚，大家情绪低落，各个工厂越搞越坏。

12 spoke   

n.（车轮的）辐条；轮辐；破坏某人的计划；阻挠某人的行动 v.讲，谈（speak的过去式）；说；演说；从某种观点来说

参考例句：

• They sourced the spoke nuts from our company.他们的轮辐螺帽是从我们公司获得的。
• The spokes of a wheel are the bars that connect the outer ring to the centre.辐条是轮子上连接外圈与中心的条棒。

13 mutation   

n.变化，变异，转变

参考例句：

• People who have this mutation need less sleep than others.有这种突变的人需要的睡眠比其他人少。
• So far the discussion has centered entirely around mutation in the strict sense.到目前为止，严格来讲，讨论完全集中于围绕突变问题上。

14 decided   

adj.决定了的，坚决的；明显的，明确的

参考例句：

• This gave them a decided advantage over their opponents.这使他们比对手具有明显的优势。
• There is a decided difference between British and Chinese way of greeting.英国人和中国人打招呼的方式有很明显的区别。

15 toxicity   

n.毒性，毒力

参考例句：

• The hoarse grunt or squeal is characteristic of toxicity.嘶哑的哼声和叫声是中毒的特征。
• Dieldrin is related to aldrin,and its toxicity to earthworms is similar.狄氏剂与艾氏剂有关，对蚯蚓的毒性是相似的。

16 drawn   

v.拖，拉，拔出；adj.憔悴的，紧张的

参考例句：

• All the characters in the story are drawn from life.故事中的所有人物都取材于生活。
• Her gaze was drawn irresistibly to the scene outside.她的目光禁不住被外面的风景所吸引。

17 allure   

n.诱惑力，魅力；vt.诱惑，引诱，吸引

参考例句：

• The window displays allure customers to buy goods.橱窗陈列品吸引顾客购买货物。
• The book has a certain allure for which it is hard to find a reason.这本书有一种难以解释的魅力。

18 steered   

v.驾驶( steer的过去式和过去分词 )；操纵；控制；引导

参考例句：

• He steered the boat into the harbour. 他把船开进港。
• The freighter steered out of Santiago Bay that evening. 那天晚上货轮驶出了圣地亚哥湾。 来自《简明英汉词典》

19 ongoing   

adj.进行中的，前进的

参考例句：

• The problem is ongoing.这个问题尚未解决。
• The issues raised in the report relate directly to Age Concern's ongoing work in this area.报告中提出的问题与“关心老人”组织在这方面正在做的工作有直接的关系。

20 acting   

n.演戏，行为，假装；adj.代理的，临时的，演出用的

参考例句：

• Ignore her,she's just acting.别理她，她只是假装的。
• During the seventies,her acting career was in eclipse.在七十年代，她的表演生涯黯然失色。

21 intervention   

n.介入，干涉，干预

参考例句：

• The government's intervention in this dispute will not help.政府对这场争论的干预不会起作用。
• Many people felt he would be hostile to the idea of foreign intervention.许多人觉得他会反对外来干预。

22 trickiest   

adj.狡猾的( tricky的最高级 )；（形势、工作等）复杂的；机警的；微妙的

参考例句：

• Many believe this is the trickiest area to navigate. 很多人认为这是最难驾驭的领域。 来自时文部分
• Establishing confidence in a new monetary system was the trickiest part. 建立对新货币体系的信心是其最棘手的部分。 来自互联网

23 constrained   

adj.束缚的,节制的

参考例句：

• The evidence was so compelling that he felt constrained to accept it. 证据是那样的令人折服，他觉得不得不接受。
• I feel constrained to write and ask for your forgiveness. 我不得不写信请你原谅。

24 underlying   

adj.在下面的，含蓄的，潜在的

参考例句：

• The underlying theme of the novel is very serious.小说隐含的主题是十分严肃的。
• This word has its underlying meaning.这个单词有它潜在的含义。

25 killing   

n.巨额利润；突然赚大钱，发大财

参考例句：

• Investors are set to make a killing from the sell-off.投资者准备清仓以便大赚一笔。
• Last week my brother made a killing on Wall Street.上个周我兄弟在华尔街赚了一大笔。

26 relatively   

adv.比较...地，相对地

参考例句：

• The rabbit is a relatively recent introduction in Australia.兔子是相对较新引入澳大利亚的物种。
• The operation was relatively painless.手术相对来说不痛。

27 remarkable   

adj.显著的，异常的，非凡的，值得注意的

参考例句：

• She has made remarkable headway in her writing skills.她在写作技巧方面有了长足进步。
• These cars are remarkable for the quietness of their engines.这些汽车因发动机没有噪音而不同凡响。