PARIS (EGMN) – An assay that measures the number of exosomes in the blood may provide a novel means of diagnosing prostate and other cancers in the near future while avoiding the need for repeated biopsies.
Validation of the Carisome platform in more than 900 clinically relevant plasma samples showed that the test had an overall accuracy of 85% to detect prostate cancer. The test is in the late stages of validation, and Caris Life Sciences Inc. hopes to offer the test to U.S. urologists later this year, with availability to European-based urologists shortly thereafter.
“Essentially, the meaning of this is that if you are diagnosed with high or accelerating [prostate specific antigen], this avoids or delays the next step of biopsy, which is painful or very unpleasant. This test should allow the detection of and differentiation between real cancer and benign prostatic hypertrophy” said Dr. Jonathan Knowles, explaining how the test works to attendees at the Worldwide Innovative Networking in Personalized Cancer Medicine Symposium.
“All cells have three main ways in which they communicate,” said Dr. Knowles, chief scientific officer of Caris. “They send out hormones, such as estrogen, or other small molecules, such as acetylcholine, or interleukin-6. They communicate via cell-to-cell contact. And they send out exosomes.”
Exosomes are released from various cell types, and are found under both normal and pathological conditions, including cancer, he continued. “They are constructed in the endoplasmic reticulum, and they are specifically used by cells to communicate with other cells,” said Dr. Knowles, who is also a professor of translational medicine at the École Polytechnique Fédérale de Lausanne (Switzerland) and holds a distinguished professorship in personalized health care at the Finnish Institute for Molecular Medicine in Helsinki.
He noted that exosomes are involved in the process whereby antigens are presented by dendritic cells to other cells in the immune system, and that they contain both micro and messenger RNA and are possibly used by cancer cells to “reprogram” other cells.
The Carisome platform is able to detect the almost 10-fold excess levels of exosomes in the plasma of patients with prostate cancer, compared with controls, and it has been shown to have 85% sensitivity and 86% specificity, based on 933 samples.
“From about 0.5 mL of blood, this particular assay can detect tumors of around 1 cm in size.” Dr. Knowles said, adding that early indications suggest that variations of the test will be of value in the detection of other tumor types, such as colorectal, breast, lung, and ovarian cancers.
“Not only can you say that somebody’s got cancer; you can also say what kind of cancer they have got,” he said.
Although the price of the test is still to be determined, Caris hopes to introduce the Carisome platform in the United States as a CLIA (Clinical Laboratory Improvement Amendments) lab-developed test. In parallel, the company is preparing to submit the test for U.S. Food and Drug Administration and European Medicines Agency approval. The first test will be for prostate cancer, with assays for other tumor types to follow.
The imminent availability of the test raises questions about its usefulness and the review process for diagnostic tests, according to Dr. Richard L. Schilsky, a professor of medicine and chief of hematology/oncology at the University of Chicago.
“If this is a CLIA laboratory test, then this would mean that any approved hospital laboratory in the United States could decide to offer the test, and any physician could order it, even though the test may not necessarily be proven to be useful for clinical decision making,” he said in an interview.
Dr. Schilsky, a former president of the American Society of Clinical Oncology and one of the scientific cochairs of the WIN (Worldwide Innovative Networking in Personalized Cancer Medicine) Consortium, noted that a prepared assay kit would need to go through FDA review. But he observed that this would focus primarily on the analytical and clinical validity of the test (“Can the test perform in a way that it can distinguish between different groups of individuals?”) rather than on its clinical utility (that is, “knowing that the test results can actually inform clinical decisions and result in better patient outcomes”).
“This is a situation where regulatory approaches are becoming more stringent, and clinicians are becoming increasingly confused. There are many different tests available, and many doctors are really unclear about what the test is good for, whether or not they should order it, and how they should interpret the results, because in many cases there are not sufficient clinical data to back up the test,” he said.
Dr. Knowles is vice chair and chief scientific officer of Caris Life Sciences, the developer of the Carisome platform.
Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
巴黎(EGMN)——在不久的将来，一种测量血液中胞外体(exosomes)数目的试验将有望成为诊断前列腺癌或其他癌症的新方案，与此同时，该方案还不需要反复进行组织活检。
研究者在超过900份临床相关血浆样本中对Carisome平台(Carisome platform)进行了验证试验，结果表明，该试验用于检测前列腺癌的总准确度达到85%。对该试验所进行的验证已经进入后期阶段，Caris生命科学公司希望在今年晚些时候向美国的泌尿科医师提供该检测方案，在此后不久，该公司还将向以欧洲地区为主的泌尿科医师提供该检测方案。
Jonathan Knowles 博士在肿瘤个体化医疗高峰论坛(Personalized Cancer Medicine Symposium)之全球化创新网络(WIN)上向与会者解释该检测的工作原理时说：“从本质上来讲，接受该检测的意义在于，如果你被诊断出体内前列腺特异性抗原的浓度过高或正不断增高，那么接受该检测可以使你避免或延缓接踵而至的组织活检，组织活检是一种令人痛苦或极其不快的检查。该检测应该有能力检测并区分真正的癌症和良性前列腺增生”。
Caris 公司的首席科学官Knowles博士说：“所有细胞均采用如下3种主要方式进行信息传递，它们可以对外分泌激素(如雌激素)或其他小分子物质(如乙酰胆碱或白细胞介素-6)。它们还可以通过细胞-细胞间的直接接触来传递信息。此外它们还可以通过分泌胞外体来介导这一过程”。
他继续道，多种不同类型的细胞均可释放胞外体，其在生理或病理状况(包括癌症)下均可检出。Knowles 博士说：“细胞通过内质网合成胞外体，并将其特异性用于介导与其他细胞间的信息传递”。Knowles 博士同时还兼任瑞士洛桑联邦理工学院转化医学系教授，且其还是芬兰赫尔辛基分子医学研究个性化医疗保健方向的知名教授。
他指出，胞外体参与了树突状细胞向免疫系统其他细胞进行抗原提呈的过程，且其同时含有小分子RNA(miRNA)和信使RNA(mRNA)，肿瘤细胞可能利用胞外体的这一特性对其他细胞进行“重新编程”。
研究者通过Carisome平台检测发现，前列腺癌患者血浆内胞外体的浓度比对照组患者高出10倍，基于933例血浆样本的检测结果表明，该检测方案的灵敏度和特异性分别为85%和86%。
Knowles博士说：“这一特定检测方法只需0.5 ml血液就能检出大约1 cm大小的肿瘤”，他补充说，早期迹象表明，在对该检测方案进行调整后，其在用于其他类型肿瘤(譬如结肠癌、乳腺癌和卵巢癌) 的检测时也具备价值。
他说：“你不但可以判断出某人已罹患癌症，你还可以判断出他们所患癌症的种类”。
尽管该检测的价格尚未确定，但Caris公司希望将Carisome平台作为CLIA(临床实验室改进修正案)实验室开发检测项目引入美国，该公司正准备就该检测方案向美国食品药品管理局(FDA)和欧洲药品管理局(EMA)申请批准。首项检测将被用于检测前列腺癌，用于检测其他类型肿瘤的方案也将陆续发布。
芝加哥大学血液肿瘤学系主任兼教授Richard L. Schilsky博士说，该检测方案即将迅速投入使用引发了种种质疑：该检测是否具备实用性？针对诊断性检测的审查过程是否严谨？
他在一次访谈中说：“如果该检测获得CLIA实验室检测项目资格，那么，这就意味着，在美国任何一家合法运营医院的实验室都有权决定是否为患者提供该检测，这还意味着，任何一位医生都可以要求患者接受该检测，即使我们可能无法确证该检测对临床决策的实用性”。
美国临床肿瘤协会前任主席，WIN(肿瘤个体化医疗之全球化创新网络)联盟副主席Schilsky博士指出，任何一种预先准备好的检测试剂盒都必需通过FDA的审查。但他评论说，这一审查将主要侧重于该检测在分析能力和临床使用方面的有效性(“该检测在使用时能否区分不同类别的患者个体呢？”)，而不是其临床实用性(即，“该检测结果所提供的信息是否确实可以影响临床决策，并改善患者的转归呢？”)
他说：“在当前形势下，管理法规正变得越发严格，而临床医生也变得越发困惑。有许多不同类型的检测可供医生使用，许多医生确实不清楚何种检测对患者有益，是否应该要求患者接受该检测，及他们应该如何解释检测结果，因为在许多情况下，该检测都没有获得足够的临床数据支持”。
Knowles博士是Caris生命科学公司的副主席兼首席科学官，同时也是Carisome平台的研发者。
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