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更新时间:2020-2-11 9:09:46 来源:本站原创 作者:佚名 浏览:

Study Points to Tighter Pairing of Drugs and Cancer Patients

The first large and comprehensive study of the genetics of a common lung cancer finds that more than half the tumors from that cancer have mutations that might be treated by new drugs that are already in the pipeline or that could be easily developed.


For the tens of thousands of patients with that cancer — squamous cell lung cancer — the results are promising because they could foretell a new type of treatment in which drugs are tailored to match the genetic abnormality in each patient, researchers say.


“This is a disease where there are no targeted therapies,” said Dr. Matthew Meyerson of the Dana-Farber Cancer Institute, referring to modern drugs that attack genetic abnormalities. He is a lead author of the paper, with more than 300 authors, being published online in the journal Nature on Sunday. “What we found will change the landscape for squamous cell carcinoma. I think it gives hope to patients,” he said.

“这是一种没有针对性治疗方案的疾病,”丹娜-法伯癌症研究所(Dana-Farber Cancer Institute)的马修·迈耶森博士(Matthew Meyerson)提及那些可以治疗基因异常的现代药物时说。他是周日发表在《自然》(Nature)杂志网站上的该文章300多名作者中的主要作者。他说,“我们的发现将改变鳞状细胞癌的格局。我觉得这赋予了病人希望。”

The study is part of the Cancer Genome Atlas, a large project by the National Institutes of Health to examine genetic abnormalities in cancer. The study of squamous cell lung cancer is the second genetic analysis of a common cancer, coming on the heels of a study of colon cancer. The work became feasible only in the past few years because of enormous advances in DNA sequencing that allow researchers to scan all the DNA in a cell instead of looking at its 21,000 genes one at a time. The result has been a new appreciation of cancer as a genetic disease, defined by DNA alterations that drive a cancer cell’s growth, instead of a disease of a particular tissue or organ, like breast or prostate or lung.

该研究是美国国立卫生研究院(National Institutes of Health)为研究癌症的基因异常而发起的大型项目癌症基因组图谱(Cancer Genome Atlas)中的一部分。对鳞肺癌的研究是继结肠癌之后,对常见癌症的第二个基因分析项目。这项工作仅在最近几年才得以成为可能,因为脱氧核糖核酸(DNA)测序领域取得的巨大进步使得研究人员可以扫描细胞里的所有基因,而不是每次只能看到2.1万个基因中的某一个基因。该项研究的结果为我们带来了对癌症的最新理解,即癌症是一种基因疾病,其特点是激发癌细胞生长的DNA变异,而不是乳房、前列腺或肺部等人体特定组织或器官的疾病。

And, in keeping with the genetic view of cancer, in this study of squamous cell lung cancer, no one mutation stood out — different patients had different mutations.


As a result, the usual way of testing drugs by giving them to everyone with a particular type of cancer no longer makes sense. So researchers are planning a new type of testing program for squamous cell cancer that will match the major genetic abnormality in each patient with a drug designed to attack it, a harbinger of what many say will be the future of cancer research.


Squamous cell lung cancer, second in frequency only to adenocarcinoma of the lung, kills about 50,000 people each year. That is more than are killed by breast cancer, colon cancer or prostate cancer. While as many as 30 percent of adenocarcinoma patients never smoked, well over 90 percent of squamous cell cancer patients are or were smokers.


Adenocarcinoma of the lung also can be easier to treat than squamous cell cancer. About 30 percent of adenocarcinoma patients have mutations in their cancers that can be targeted by new drugs. Those drugs do not work in squamous cell cancers, whose mutations are different.


The new study compared tumor cells from 178 squamous cell lung cancer patients to the patients’ normal healthy cells. More than 60 percent of the tumors had alterations in genes used to make protein and lipid kinases, enzymes that are particularly vulnerable to the new crop of cancer drugs and for which many drugs are already available or are being tested in other cancers.


Kinases, explained Dr. Roy S. Herbst of Yale Cancer Center, who was not an author of the new study, function like on-off switches for cell growth. When they are mutated, the switches are stuck in an on position. About a dozen companies, he added, have drugs that block mutated kinases.

耶鲁大学癌症研究中心(Yale Cancer Center)的罗伊·S·赫布斯特(Roy S. Herbst)博士(不是新研究的作者)解释说,激酶对细胞的成长起着开关的作用。一旦激酶发生突变,开关就会卡在开的位置。他补充说,大约有12家公司研制出了可阻挡突变激酶的药物。

Yet even though the squamous cell cancers analyzed in the study often had kinase mutations, cells have many kinase genes and the mutations were different in different patients.


“Unfortunately, what the Cancer Genome Atlas has revealed is that everyone’s cancer could be very different, said Dr. William Pao, a lung cancer researcher at the Vanderbilt-Ingram Cancer Center and an author of the new paper. “The field is really moving toward personalized medicine.”

“不幸的是,癌症基因组图谱表明,每个人的癌症都可能是非常不同的,” 新论文作者之一、范德比尔特-英格拉姆癌症中心(Vanderbilt-Ingram Cancer Center)的肺癌研究员威廉·保(William Pao)说道。“该领域正在真正迈向个性化医学。”

The study also found a real surprise, Dr. Meyerson said, something that had not previously been seen in any cancer. About 3 percent of the tumors had a gene mutation that might allow them to evade the immune system. By coincidence, an experimental drug that unleashes the immune system was recently tested in lung cancer patients. Some of those who did not respond might have the mutation, he said.