为了赶上国际步伐、增强我国临床及科研工作者对液体活检的认知，10月中旬，在上海交通大学施奇惠教授和苏州浚惠生物阎灼辉先生的大力邀请下，液体活检领域的学术领军人物——“液体活检之父”、德国汉堡大学肿瘤生物学中心主任Klaus Pantel教授和法国蒙皮利埃大学LCCRH研究室主任Catherine Alix-Panabières教授一同来到中国，在上海与上海市胸科医院陆舜教授等专家，在北京与国家癌症中心、中国医学科学院肿瘤医院药物临床试验研究中心的李宁教授等中国专家就“液体活检”的国际经验，和中国研究应用现状进行了广泛地交流。
Klaus Pantel教授和Catherine Alix-Panabières教授
“非常荣幸，我们这次邀请到了Pantel教授和Alix-Panabières教授到上海和北京访问，并且由两位专家牵头的第1届The Liquid Biopsy Conference (暨第12届微小残留癌国际研讨会International Symposium on Minimal Residual Cancer, ISMRC）也决定将于2020年首次在中国上海举办。”
1st TLBC2020 大会
ISMRC大会由Pantel教授于1996年创立，每两年在世界各地举办一次，旨在将液体活检的最新研究进展传播向全球各个国家。如今，ISMRC已经走过旧金山、大阪、慕尼黑、柏林、奥斯陆、汉堡、巴黎等地，今年的第11届ISMRC也于5月初在法国南部的蒙皮利埃成功举办。作为Liquid Biopsy概念的首先提出者，Pantel教授希望2020年的大会开始使用The Liquid Biopsy Conference 的名字，并且会包括更多肿瘤以外的领域。
1. Nowadays, liquid biopsy has attracted more and more attention from the clinical researchers. Could you please give us a general introduction on the development of liquid biopsy?
Liquid biopsy is the detection of tumor cells and tumor cell products in the blood, and it is complimentary to tissue biopsy. As we know, sometimes it's very difficult to get a tissue biopsy from a tumor of a patient, because the tumour may be located in the lung or in the brain, and in the lung it's not so easy to put a needle in.
About ten years ago, there have been substantial technical developments allowing us to look into the blood. Take a blood sample and see whether you get the same information that you usually get from a needle biopsy from a tissue sample, and this information can be then very helpful to treat the patient better. Because the treatment is based on the individual information that is taken from the blood sample of this particular patient.
2. At present, which detection methods are the most studied, and may show a promising application prospect?
I think that these methods are complimentary. You can have circulating tumor cells (CTCs) and get information on the protein content of these tumor cells, also can measure the RNA content of the circulating tumor cells. Then you can get information on resistant pathways like the antigen receptor resistance pathway.
And you can also look at the DNA, like cell free DNA (cfDNA), and at the DNA you can look for mutations that are relevant to therapy. Like mutations of the EGFR gene, which are very important in lung cancer particular in China, as many lung cancer patients have these mutations in China, and there are EGFR-TKIs that targeting these mutations.
Besides you can look at resistance mutations. Sometimes when the standard therapy treating the patients does not work anymore, the reason is that the tumour has changed and has acquired new mutations. You can detect them and give another drug and maybe a third drug or forth drug. And all these drug treatments are based on the analysis of your circulating DNA or your CTCs. And that, I think is probably the future of precision medicine.
3. What are the largest advances in liquid biopsy worldwide?
I think the largest advances are on one hand at the technology. In the last ten years, we have received very sensitive methods and very precise method to capture CTCs, and also to analyze them. And we have also developed next generation sequencing methods that allow us to look really into DNA very specifically for mutations.
And these methods have been even refined, so that you can detect very small amounts of tumour DNA in a sea of normal DNA, and pick up a few tumor cells in a sea of million of normal blood cells. And this kind of technical developments in the CTC but also in the cfDNA field has really made it possible to measure these things in cancer patients, and then related to the outcome in the clinical studies, and of course the studies are very important to validate these new technologies.
4. And how will the liquid biopsy change the clinical practice, in what aspects?
I think the liquid biopsy have different application areas. One area is early detection of tumour. It would be fantastic if lung cancer can be detected earlier, and not only when the patients have some symptoms like having a cold. Thus, early detection of cancer is one of the applications.
Then, you want to find out which patients have a risk to develop a relapse after surgery. There’s no tumor after surgery, but there might be some tumor cells in the body that the radiologist can not see. If you take a blood sample every three or six months, you may see that a patient is having a recurrence of tumour, or a tumour comes back as metastasis in another organ.
And the third application is that we identify therapeutic targets and persistent mechanisms through the CTCs, but also the ctDNA, and then we can find out which patient needs which kinds of therapy. So we can make it individualized. As every patient has a bit of different tumour, we have to know exactly the characteristics of this tumor.
5. And in the worldwide, are there any products related to liquid biopsy coming into the clinic now?
I think the ctDNA or cfDNA measurement for the EGFR mutations has been accepted in many countries. The patients with lung cancer can take a blood sample and you can see from the blood whether they have mutations in the EGF receptor gene, so that you can give certain drugs that is already approved.
And there are also new applications coming into the place, using CTCs for monitoring or for deciding therapies. So I'm quite optimistic that within the next two to five years we have more of those clinically approved applications.
6. What are the challenges of liquid biopsy？
One of the challenges is that, we have to use very, very sensitive methods. You have to make sure that the methods are all still very specific. Because if you're very sensitive, you may find something that is not relevant to the clinic. For example, if people get older or smoke a lot, they may have a lot of mutations in their blood in the DNA, it may not mean the necessarily of all the mutations. So we have to be careful, and our technologies will become more and more sensitive.
And another challenge is to find out how the technology helps us to cure more patients or to treat patients better. We have to say to the doctor in the clinic, okay, now you have to change your treatment because our mark on the blood assays said something. The drug is not working, some other drug should work. But in order to really prove that concept works, we have to show that the patients live longer.
Sometimes it's not easy to say yes, if one therapy doesn't work, you have to change to another one, but maybe the other one also doesn't work. And then you know it's not good. Thus, you have to show that the biomarker has some clinical utility, which means that it's helpful for better treatment of the patients, better management of the patients.
But that is not so easy. It takes long clinical studies to achieve good development and it requires very robust assays. And the assays need to be reproducible, they have to measure exactly the same. So you need those good assays, but you also need very good clinical studies. You have to bring them together, these are the challenges.
7. The ISMRC 2020 will be held in China, could you please introduce the background and the intention of the conference?
I start to organize this conference in nineteen ninety-six, more than twenty years ago. And we have this conference every two years all over the world. We had the congress this year in Montpellier in the south of France. In fact, the conference has been held in San Francisco, Osaka, Munich, Berlin, Oslo, Athens, Hamburg, Paris and so on. So we really disseminated this Symposium through the world and it would be the first time that we will organize this conference in China.
The Shanghai meeting would be the first one in China which is fantastic, because there's a lot of activity in China going on in medicine and also in the liquid biopsy field. So we are very happy actually to have this conference two years from now in the beautiful city of Shanghai.
8. what's your opinion on promoting the development of liquid biopsy in China and around the world through the conference?
I think what I want is really that when I retire ten years from now that liquid biopsy has been introduced in the clinic. I have more than four hundred publications on liquid biopsy. I do not need more publications, but I would be more satisfied if any of the liquid biopsy tests are really more and more accepted in the clinic.
By disseminating this information how to use it and what needs to be done to bring it in the clinic in the entire world, I hope that it will get accepted throughout the world, and not only in Germany or only in China, or only in the US. This is really my wish that different countries participate on this very successful story.
9. Professor Catherine Alix-Panabières, here, I also have a question for you. And we know you are also committed to liquid biopsy and have achieved many good research findings, could you please talk about the latest progress in the field of liquid biopsy. And what do you think of the prospects for liquid biopsy?
As Klaus Pantel just said that it's very important to have sensitive and robust methods to detect CTCs and all the other circulating biomarkers. It's really what we have done during the last decade. But the important thing is to prove now that their clinical validity and clinical utility.
Indeed, we have to prove in the different clinical trials that there is a benefit for the patients. It's really what I expect for the next year, that more and more interventional clinical trials can really show that there is a clinical utility for the liquid biopsy. And also what I believe is that we have to combine CTCs, ctDNA but also exosomes, microRNA, tumor-educated platelets to get a full picture of cancer as well as the immune system of each cancer patient.
Thus, all together, we can have a more precise view of the cancer progression or even cancer detection, because we will have information from the different circulating biomarkers. It's a very big family of different biomarkers now, and we need to really see everything as complimentary more than competitive thing.
在浚惠生物创始人阎灼辉、首席科学顾问施奇惠的邀请下，“液体活检之父”、德国汉堡大学肿瘤生物学中心主任Klaus Pantel教授，法国蒙皮利埃大学LCCRH研究室主任Catherine Alix-Panabières教授来到中国，与国内业界顶尖专家交流液体活检的国际经验和中国研究应用现状。