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日期：2015年4月22日 来源：麻省理工学院科赫综合癌症研究所 原作者：Anne Trafton 好医友（Haoeyou）编译（转载请标注来源）
目前有超过100种的药物被批准用于癌症治疗，但是对于特定患者哪种药最有帮助，目前来说还是不精确的。一个新型的植入式设备可能会改变这种状况。 麻省理工学院研发的一种新设备可能会改变这种状况。米粒大小的植入式装备可以携带多达30种的不同小剂量药物。在肿瘤中植入后，让药物扩散到组织，研究人员可以衡量每一种药物杀死患者癌细胞的效果。
“这种装置可以在选择癌症治疗方案时，摒除掉目前很多的推测性工作”，麻省理工学院科赫综合癌症研究所博士，兼该设备论文（发表于4月22日《科学转化医学》期刊）的主要作者奥利弗·乔纳斯说。
“你可以用它来测试患者的各种可用药物，然后选择效果最好的一种。”乔纳斯说。
这篇论文的资深作家有罗伯特·兰格——麻省理工学院大卫·H·科赫研究所教授，科赫研究所及医学工程和科学研究所和化学工程系的一员；迈克尔·西玛——麻省理工学院大卫·H·科赫研究所教授，科赫研究所和材料科学与工程系的一员。
Putting the lab in the patient 对病人进行试验
大部分癌症常用药，是通过破坏DNA或从其他方面干扰细胞功能来起作用的。近期，科学家们也开发了更具针对性的药物来杀死携带特定基因突变的肿瘤细胞。但是，通常很难预测某个特定的药物是否对特定个体患者有效。
在一些例子中，医生提取肿瘤细胞，在实验室培养皿培养然后用不同的药物治疗观察哪一个是最有效的。但是，这个过程是将细胞从它们的自然环境中移走，而这个环境对于肿瘤如何回应药物治疗是发挥重要作用的，乔纳斯说。
“我们认为比较好的方法就是直接在患者身上进行试验”，他说，“这很安全，你可以在这种自然的微环境中做所有的灵敏度测试。”
该设备由硬结晶聚合物制成，可以通过活检针植入患者的肿瘤。在植入后，药物渗透进肿瘤200到300微米，但是不会彼此重叠。任何类型的药物可以进入该储层，并且研究人员可以制定药物，以便使到达癌细胞的剂量类似于通过典型给药方式，如静脉注射，能够给予的量。
一天的药物接触后，植入物以及其周围的小块肿瘤组织样本被移除，研究人员对组织样本进行切片分析和用能够检测到细胞死亡标记物或扩散标记物的抗体进行染色。
Ranking cancer drugs 对抗癌药物进行排名 为了检测该装置，研究人员将它植入在嫁接了人类前列腺肿瘤，乳腺肿瘤，黑色素瘤的老鼠身上。众所周知，这些肿瘤对于不同的癌症药物有不同的敏感性，而麻省理工学院的研究小组所得出的结论与之前那些差异结果是一致的。
然后研究人员针对三阴性乳腺癌来测试该设备，这类癌症缺少了乳腺癌三个最常见的标记物：雌激素受体，孕激素受体和人类表皮生长因子受体。这种形式的癌症侵袭性很强，对它使用的药物中，没有一个是针对特定基因标记物的。
使用这个设备，研究人员发现三阴性肿瘤对五种常用治疗药物的反应不同。最有效的是紫杉醇，其次是阿霉素、顺铂、吉西他滨和拉帕替尼。他们通过静脉注射这些药物时也得出了相同的结果，这表明了该设备能准确预测药物的敏感性。
在这个研究中，研究人员是将每个药物单独进行比较，但是该设备也可以检测不同的药物组合，即通过将两种或三种药物放进相同的储层即可，乔纳斯说。
这个设备可以在系统性化疗开始之前，帮助我们确定每个肿瘤最好的化疗药物和组合，而不是基于人口统计数据做出选择。这是肿瘤学家们长期以来的追求，同时朝着我们发展精准癌症治疗的目标迈出了重要一步”。纪念斯隆凯特琳癌症中心首席医疗官兼该论文的作者之一乔斯·巴赛格说。
研究人员目前正在研究一些方法，让该设备处于患者体内时更容易被读取，也让他们更快获取结果。他们也计划明年开设一项针对乳腺癌患者的临床试验。
该设备的其他可能应用包括指导癌症新药的开发和检测。研究人员可以针对比较有前途的化合物，创建几个不同变体，并同时在小规模人群身上做试验，选出最有效的一个变体，进行更大规模的临床试验。
附英原文：
Personalized medicine: Device identifies drugs that will work best for each patient Date:April 22, 2015 Source:Koch Institute for Integrative Cancer Research at MIT
More than 100 drugs have been approved to treat cancer, but predicting which ones will help a particular patient is an inexact science at best.
A new device developed at MIT may change that. The implantable device, about the size of the grain of rice, can carry small doses of up to 30 different drugs. After implanting it in a tumor and letting the drugs diffuse into the tissue, researchers can measure how effectively each one kills the patient's cancer cells.
Such a device could eliminate much of the guesswork now involved in choosing cancer treatments, says Oliver Jonas, a postdoc at MIT's Koch Institute for Integrative Cancer Research and lead author of a paper describing the device in the April 22 issue of Science Translational Medicine.
"You can use it to test a patient for a range of available drugs, and pick the one that works best," Jonas says.
The paper's senior authors are Robert Langer, the David H. Koch Professor at MIT and a member of the Koch Institute, the Institute for Medical Engineering and Science, and the Department of Chemical Engineering; and Michael Cima, the David H. Koch Professor of Engineering at MIT and a member of the Koch Institute and the Department of Materials Science and Engineering.
Putting the lab in the patient
Most of the commonly used cancer drugs work by damaging DNA or otherwise interfering with cell function. Recently, scientists have also developed more targeted drugs designed to kill tumor cells that carry a specific genetic mutation. However, it is usually difficult to predict whether a particular drug will be effective in an individual patient.
In some cases, doctors extract tumor cells, grow them in a lab dish, and treat them with different drugs to see which ones are most effective. However, this process removes the cells from their natural environment, which can play an important role in how a tumor responds to drug treatment, Jonas says.
"The approach that we thought would be good to try is to essentially put the lab into the patient," he says. "It's safe and you can do all of your sensitivity testing in the native micro environment."
The device, made from a stiff, crystalline polymer, can be implanted in a patient's tumor using a biopsy needle. After implantation, drugs seep 200 to 300 microns into the tumor, but do not overlap with each other. Any type of drug can go into the reservoir, and the researchers can formulate the drugs so that the doses that reach the cancer cells are similar to what they would receive if the drug were given by typical delivery methods such as intravenous injection.
After one day of drug exposure, the implant is removed, along with a small sample of the tumor tissue surrounding it, and the researchers analyze the drug effects by slicing up the tissue sample and staining it with antibodies that can detect markers of cell death or proliferation.
Ranking cancer drugs
To test the device, the researchers implanted it in mice that had been grafted with human prostate, breast, and melanoma tumors. These tumors are known to have varying sensitivity to different cancer drugs, and the MIT team's results corresponded to those previously seen differences.
The researchers then tested the device with a type of breast cancer known as triple negative, which lacks the three most common breast cancer markers: estrogen receptor, progesterone receptor, and Her2. This form of cancer is particularly aggressive, and none of the drugs used against it are targeted to a specific genetic marker.
Using the device, the researchers found that triple negative tumors responded differently to five of the drugs commonly used to treat them. The most effective was paclitaxel, followed by doxorubicin, cisplatin, gemcitabine, and lapatinib. They found the same results when delivering these drugs by intravenous injection, suggesting that the device is an accurate predictor of drug sensitivity.
In this study, the researchers compared single drugs to each other, but the device could also be used to test different drug combinations by putting two or three drugs into the same reservoir, Jonas says.
"This device could help us identify the best chemotherapy agents and combinations for every tumor prior to starting systemic administration of chemotherapy, as opposed to making choices based on population-based statistics. This has been a longstanding pursuit of the oncology community and an important step toward our goal of developing precision-based cancer therapy," says Jose Baselga, chief medical officer at Memorial Sloan Kettering Cancer Center and an author of the paper.
The researchers are now working on ways to make the device easier to read while it is still inside the patient, allowing them to get results faster. They are also planning to launch a clinical trial in breast cancer patients next year.
Another possible application for this device is to guide the development and testing of new cancer drugs. Researchers could create several different variants of a promising compound and test them all at once in a small trial of human patients, allowing them to choose the best one to carry on to a larger clinical trial.
The above story is based on materials provided by Koch Institute for Integrative Cancer Research at MIT. The original article was written by Anne Trafton. |
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