A new age of personalised treatment for prostate cancer
Spotify
Google Podcasts
Apple Podcasts
Transcript
CORDIScovery podcast- Episode #38 - A new age of personalised treatment for prostate cancer
This is an AI transcription.
00:00:10:05 - 00:00:16:06
Abigail Acton
This is CORDIScovery.
00:00:16:08 - 00:00:41:17
Abigail Acton
Hello and welcome to this episode of CORDIScovery with me Abigail. Acton. Things are moving in the world of prostate cancer treatment. Findings just announced from the University of Oxford show that a special type of fluorescent dye might help surgeons find areas of cancerous tissue not picked up by the naked eye or other clinical methods. A new dimension in precision surgery is how it's been described by Professor Freddy Hamdy, the lead researcher.
00:00:41:19 - 00:01:07:01
Abigail Acton
Meanwhile, a new cheap and simple testing method using saliva could help catch the disease earlier by identifying the genetic factors which make men more likely to develop the condition. A leap forward in diagnostics and in treatment would be very welcome. Prostate cancer is the second most frequent malignancy in men. In 2020 alone, around one and a half million new cases and almost half a million deaths were registered worldwide.
00:01:07:03 - 00:01:17:13
Abigail Acton
The chances of survival depend on the timing of the diagnosis. Almost half of those diagnosed will survive their prostate cancer for five years or more if it is caught at an early stage.
00:01:19:02 - 00:01:41:17
Abigail Acton
Here to talk us through about some of the latest innovations brought about through the support of EU science research funding are Jan Tkac, the founder and chief scientific officer at Glycanostics in Slovakia. The company has developed an innovative diagnostic test for cancer based on novel biomarkers. Jan is also keen to explore how different sports relate to levels of endorphin release. Hello Jan.
00:01:41:19 - 00:01:43:21
Jan Tkac
Hello. Thank you very much for the invitation.
00:01:43:23 - 00:02:00:15
Abigail Acton
Lovely to have you here. Harald Mischak is the scientific officer at Mosaiques Diagnostics and Therapeutics AG Germany. He is focused on understanding the underlying molecular structures of certain types of cancers to identify the most appropriate therapeutic targets and drugs. Welcome.
00:02:00:17 - 00:02:02:13
Harald Mischak
Hello. Nice to be here.
00:02:02:15 - 00:02:20:05
Abigail Acton
Excellent. Joaquin Mateo, who is group leader at the Translational Research Group in Prostate Cancer at the Vall d’Hebron Institute of Oncology in Barcelona. He is also medical oncologist at the Aldebaran University Hospital. Joaquim is especially interested in the development of novel forms of precision medicine. Hello, Joaquin.
00:02:20:07 - 00:02:22:07
Joaquin Mateo
Hello Abigal and to everyone listening.
00:02:22:11 - 00:02:35:22
Abigail Acton
Jan, I'm going to start with you, if I may ask. ProSCAN developed an innovative glycan based early diagnostic method for prostate cancer. So can you explain what Glycans are and why are they interesting at the scientific community at the moment.
00:02:35:24 - 00:03:04:11
Jan Tkac
Thank you very much. So glycans are complex carbohydrates attached to proteins or lipids and actually glycans are present on every single cell in our body. And actually it's estimated that up to 70% of all proteins in our body are glycans oscillated. So glycans are able to provide really very useful information about physiological status of the cell. So this is one way how glycans can be used.
00:03:04:13 - 00:03:19:15
Jan Tkac
And the other one is the fact that glycans can also provide information about a development of some diseases or progression of some diseases, including cancer. And actually, this is why we are using glycans as cancer biomarkers.
00:03:19:17 - 00:03:32:04
Abigail Acton
Okay. All right. They give an accurate picture of the status of what's going on. So the ProSCAN project was hosted by your firm Glycanostics. So what's novel about your approach? Because I know scientists are interested in Glycans. What are you doing differently?
00:03:32:06 - 00:04:09:04
Jan Tkac
Okay, so actually what we are doing, we are looking at a specific glycan on specific proteins. For example, in case we would like to diagnose prostate cancer, we are looking on the differences in the glycan composition on one protein in our case its PSA, its prostate specific antigen. So how does it work? So actually, we are working in serum samples, a very complex sample containing hundreds of different proteins or glycoproteins and DNA and other molecules.
00:04:09:06 - 00:04:37:17
Jan Tkac
And actually we're using magnetic particles modified by antibodies. And actually those antibodies are able to selectively interact only with PSA molecule in this complex sample. So then these PSA molecules actually also attach to magnetic particles. Then we are using really small magnets for separation of magnetic particles and everything is washed away. And in the final step, we are using other proteins collecting.
00:04:37:20 - 00:05:06:18
Jan Tkac
And those like these are able to selectively interact with some glycan structures. And actually we are using information about differences in glycan structure for diagnosing of many diseases. So on one side we are using PSA, which is tissue specific, and on the other side we are using analysis of glycans, which are cancer specific. So by combining, we can then accurately diagnose, for example, prostate cancer.
00:05:06:20 - 00:05:23:13
Abigail Acton
Okay, this is fantastic. So basically the magnetic particles attached to the blood cancer you're interested in, and you can extract those simply by extracting the magnetic particles and they follow. That's fabulous. And is it a complex test to run? Do you have to use new equipment, specialist laboratories or?
00:05:23:16 - 00:05:52:24
Jan Tkac
No, no, actually, it's very simple. So it works in a laser format. It's very complicated named. So it's enzyme linked immunosorbent assay. But actually, this assay is very, very simple. So it runs only using ordinary equipment. We call it a laser reader. Actually, this reader is in many different laboratories worldwide, and actually it's also in clinical laboratories. So there is no need to use some special infrastructure.
00:05:53:01 - 00:06:14:11
Jan Tkac
What is really needed? It's to use only, only a laser reader, and they actually do it. So using magnetic beads, it's very, very simple. So magnetic beads allows us to work with, for example, PSA protein attached to magnetic beads. We don't need, for example, to release PSA from the magnetic beads and then to analyze this PSA separately.
00:06:14:14 - 00:06:31:22
Jan Tkac
Everything can be done on the surface of magnetic beads. So assay is very simple. It can be done in short time. And also, we can then use really small amount of our sample. For example, few drops of blood serum is really sufficient for the analysis.
00:06:32:01 - 00:06:46:08
Abigail Acton
Yes, obviously. I mean one of the problems with cancer generally, but with prostate cancer is the necessity for biopsies which can be, you know, tricky to achieve. They're expensive and there can be side effects and so on. And I believe that your technique greatly reduce the need for that sort of tissue.
00:06:46:10 - 00:07:12:24
Jan Tkac
So actually we are working with serum samples. So this means that our approach is early stage cancer diagnostics. And this is really needed because, for example, an urologist needs to manage patient properly, for example, to suggest should this patient needs to undergo a biopsy or no. And actually our test can provide second opinion to guide urologist.
00:07:12:24 - 00:07:30:23
Jan Tkac
If patient needs to undergo a biopsy. And actually, in last clinical validation study, when we showed that our test is the best path from all surgical tests which are currently available on the market, and actually we could significantly reduce number of biopsies using our test.
00:07:31:00 - 00:07:49:24
Abigail Acton
Excellent, which is stress and money and time, which is obviously crucial and in the case of diagnosis for cancer. And how is the system working in practice? So is your system of analysis actually in place in certain health centers and environments in hospitals? Or when could people expect to be able to benefit from this innovation?
00:07:50:01 - 00:08:16:21
Jan Tkac
So actually, when is in a laser format, and it's very easy to transfer this technology also on highly automatic machines of industry leaders. And actually in our case, since we are using magnetic particles in our assay this transfer is more convenient for big diagnostic or pharma companies at a later stage, because all those early automatic machines actually involve the use of magnetic particles.
00:08:17:02 - 00:08:36:09
Jan Tkac
So this is going to be beneficial in our case. And currently we are in Slovakia running testing. So actually we have some agreement with urologists in Slovakia so patients can pay for this kind of service and urologists can provide really very useful information on how to manage the patient.
00:08:36:11 - 00:08:40:09
Abigail Acton
Okay, that sounds wonderful. You must be very proud of all the work that you've achieved so far.
00:08:40:11 - 00:08:52:06
Jan Tkac
Yeah, it was really hard work. Yes, but it's good that this test can be actually used. So we started in Slovakia and we would like to extend use of this test in other countries as well.
00:08:52:07 - 00:09:01:02
Abigail Acton
Yeah, of course. Absolutely. And how long did it take you to develop this system? Because it must have been a long time in the pipeline.
00:09:01:07 - 00:09:30:01
Jan Tkac
Yes, Actually, it started with an ERC grant. It was in 2012. Then in 2017, we established a company, but then it took quite significant time, for example, to get finances and an investment and fully develop the product. So from the start of the company, it's almost seven years now. So it was quite a long journey. But yeah, it was a really nice experience.
00:09:30:03 - 00:09:50:17
Abigail Acton
But now finally you actually going to see the benefit when it comes out. I think that's wonderful. Thank you so much. That was a very interesting explanation and beautifully set up. Thank you for that. I'm going to turn to Harald please. Harald as drugs act on a molecular level. The molecular differences between patients means that while a drug can benefit some, it might not be effective for all.
00:09:50:19 - 00:10:07:02
Abigail Acton
PCaProTreat wanted to unravel this for better diagnosis and treatment. So Harald, like Jan your project, also considered less invasive ways of diagnosis in this case noninvasive urinary biomarkers that enable early detection of prostate cancer. Can you tell us more about this form of analysis first?
00:10:07:08 - 00:10:37:01
Harald Mischak
Yeah, that was developed out of a project to basically identify different diseases based on urinary peptides. We have to consider that in general, all smaller proteins and peptides are present in the engineering, so whatever is in circulation will be filtered, they'll be in urine and urine has two main advantage from a technical point of view that it's quite stable, that urine has been stored in the bladder for several hours at 37 degrees.
00:10:37:03 - 00:10:44:12
Harald Mischak
So whatever we can detect in there is stable and can therefore also be shaped among all sampling issues.
00:10:44:14 - 00:10:45:07
Abigail Acton
Okay.
00:10:45:09 - 00:10:59:16
Harald Mischak
It works quite well for kidney, cardiovascular disease. And then we also played it for prostate cancer, among other cancers, and found there are many specific proteins and peptides in urine that indicate the presence of cancer.
00:10:59:22 - 00:11:09:12
Abigail Acton
Okay. So I know that your project gathered molecular proteomics data from thousands of prostate cancer patients. So what did that enable your team to do?
00:11:09:14 - 00:11:37:21
Harald Mischak
To identify which proteins and peptides are significantly associated with cancer. As with prostate cancer in this way, which proteins are indicative of aggressive cancer, you may consider that most prostate cancer patients do not die from the counts but with the cancer. That is a big issue. So in most cases I would also argue it would be better for the patients not even knowing that they have cancer if they can't do anything anyway.
00:11:37:23 - 00:12:06:04
Harald Mischak
Anyway, these proteins in the end are to some degree also responsible for the cancer. So therefore they form. If you want to say that the molecular basis of the cancer, knowing these proteins means I know where exactly to interfere. And using all this information theoretically on all of the properties of the changed, I can predict which molecules, drugs or whatever I can use to revert these changes, basically.
00:12:06:06 - 00:12:16:16
Abigail Acton
Okay. So it's like a comprehensive profile of the particular cancer that the patient has gives you all the like a real thorough painting, like a portrait of a particular cancer.
00:12:16:18 - 00:12:32:12
Harald Mischak
Yes. Also, I can't say it's not it's not a cancer sort of speaking of, cancer is quite heterogeneous. And this micro heterogeneity in cancer really is the big problem. But typically, cancer cannot be cured easily.
00:12:32:14 - 00:12:42:06
Abigail Acton
Right. And I know that your project was really looking at a multi-omics approach. Can you explain what a multi-omics approach is? And I believe it's quite innovative.
00:12:42:08 - 00:13:11:09
Harald Mischak
There are different so-called omics techniques, proteomics, investigating proteins, transcriptome omics investigate the DNA transcripts that are called the proteins, genomics investigating the DNA and so on. All of these have in common that they investigate thousands of different molecules and some of these are changed in disease. And together they of course are able to let's take even more comprehensive picture of the specific disease.
00:13:11:15 - 00:13:22:14
Abigail Acton
Right. Okay. So it's like a holistic approach. And then, of course, you end up with a huge amount of data. So, there has been computational work on in your project as well.
00:13:22:16 - 00:13:49:24
Harald Mischak
Yes, there is plenty of computational work involved. Obviously plenty of experts, and certainly the work has profited a lot from collaboration with multiple different scientists in the field of, let's say, bioinformatics, systems, medicine and so on. Where I come from as well. We also have benefited basically from our experience in molecular diagnostics where we run into the same problem.
00:13:50:01 - 00:14:09:20
Abigail Acton
Right. Well, I'd like to talk about the molecular diagnostics now actually. So I mean, as we've just said, cancer is a very complex structures notoriously hard to treat. So I knew that one of the things you were interested in was reverse engineering, what was going on actually to cause the cancer growth. Could you tell me a little bit more about what you meant by reverse engineering in this concept?
00:14:09:22 - 00:14:46:02
Harald Mischak
In principle, as I said, the cancer, basically any kind of disease is determined on the molecular level. You have specific molecular changes associated with disease. Some of these are in fact decisive and decide on the direction of disease. If you know these changes, you can use small molecular weight compounds or also antisense RNA, anti proteins, whatever. To revert this change, you bring the molecular signature of the cell or the accumulation of cells back to where it was before.
00:14:46:04 - 00:15:13:17
Harald Mischak
And this would imply that the disease in this case, the tumor, is also reported. This is what you would call the reverse engineering. We know about a lot of drugs and compounds, how they interfere or how they change expression of certain proteins. And then we just overlay these different patterns to predict which of the drugs may be most useful in a specific type of cancer or for a specific patient.
00:15:13:17 - 00:15:32:14
Abigail Acton
Thank you very much. That's a very clear explanation. I'm appreciating both of these fantastic explanations. So, building on these findings, you were looking for potential drug candidates. So where are you up to with this? What what did all of this analysis and complex computer work as well show you? Where does it leave us?
00:15:32:16 - 00:16:00:08
Harald Mischak
Well, now we have seven candidates, drug candidates shortlisted and these we now need to investigate in more detail. We need to demonstrate whether where we know from some of them by now that they in fact revert to tumor phenotype in cell lines, in vitro or as in the tissue culture. This is where it stops because the approach beyond is quite expensive and there is a huge regulatory burden.
00:16:00:10 - 00:16:05:04
Harald Mischak
And here, unfortunately, I have to say we have to try to find funding.
00:16:05:06 - 00:16:18:03
Abigail Acton
Yeah, we must be quite frustrating when, you know, you're sitting on something that is actually potentially really, you know, going to save lives and turn situations around and presumably not just for prostate cancer, but perhaps could be applied to other cancers as well.
00:16:18:03 - 00:16:24:09
Harald Mischak
No, you're right. It is frustrating. We have to find funding from private venture capital companies.
00:16:24:23 - 00:16:25:14
Abigail Acton
00:16:25:16 - 00:16:35:24
Harald Mischak
That’s what we are doing and all the patient organizations now support us and try to find the funding because in the end of course, the patients would benefit from an improved drug.
00:16:36:03 - 00:16:44:24
Abigail Acton
You know, potentially life saving. Absolutely. Okay. Thank you so much for explaining that so clearly. Does anyone have any comments? Yes, please. Joaquin.
00:16:45:01 - 00:17:03:10
Joaquin Mateo
I want to ask my colleagues. I mean, first of all, congratulations for your work is really amazing. But I want to ask Harald if beyond the applications for diagnostics, have you ever tested whether this urine test could actually detect a relapse of the disease on a patient that has already had surgery for their prostate tumor?
00:17:03:12 - 00:17:25:24
Harald Mischak
We have not investigated this in detail, I would assume, yes. We tested this in a slightly different context in bladder cancer where the tumor is removed. But as you know, frequently these patients develop novel or relapse of the tumor and they are be tested. And we found that, in fact, yes, we can detect the relapse of the tumor.
00:17:26:05 - 00:17:42:19
Harald Mischak
Of course, it's a matter of size also. So I would say that you cannot. It's difficult to detect the few tumor cells, but once the tumor reaches a certain size of maybe 1 to 2 millimeters, quite easy to detect using this technology.
00:17:42:21 - 00:17:58:20
Abigail Acton
Fantastic. That's excellent. That's really, really good. Like almost a thermometer, sort of keeping an eye without being invasive and again presumably as you said the urine stores well, it's easy to access. It's easy to use. Brilliant. Thank you.
00:17:58:22 - 00:18:11:07
Harald Mischak
The one advantage that these have pointed out as well is that we now have data from close to 90,000 patients with different diseases and controls. So this helps to be quite certain about the statistics behind it.
00:18:11:09 - 00:18:20:18
Abigail Acton
That's an awful lot of patients. Gosh, were they all taken? What database is this? Is this some sort of a collective database?
00:18:20:19 - 00:18:27:06
Harald Mischak
Yes, that’s a collection. We were involved in many European projects so is a collection of all of these samples and data.
00:18:27:06 - 00:18:50:01
Abigail Acton
Okay. Fabulous. I mean, that's very rich resource. Very useful. Super. Okay. Thank you so much. Joaquin I'm going to turn to you now. The AR-DDR project looked at the exchange between two key pathways involved in prostate cancer development. So you're interested in treatment. We've been looking at diagnostics now returning to treatment. You want to optimize precise therapeutic options.
00:18:50:03 - 00:18:58:15
Abigail Acton
So when you say prostate cancer, we think of one single disease. But as Jan was explaining as well, that's not quite accurate. Joaquin, can you tell us more about the condition, please?
00:18:58:17 - 00:19:21:09
Joaquin Mateo
Yes, I think that we have just added from our colleagues two brilliant studies on how to better diagnose and treat initial stages of prostate cancer. Certainly in most prostate cancer are diagnosed at the time. What that is confined to the proceeding can be cured, but we know that certain patients develop upfront an advanced prostate cancer condition.
00:19:21:09 - 00:19:45:09
Joaquin Mateo
So the cancer has spread outside the prostate to other organs. We know very well now that this what we call localized prostate cancer and what we call metastatic or advanced prostate cancer are two different biological entities, and that the molecular features of their localized or advanced cases are very different. So that's a difference.
00:19:45:09 - 00:20:26:20
Joaquin Mateo
But when we go to the field where I work on and maybe I might be biased because I work on the minority of prostate cancers that are very aggressive and had spread outside the organs, we still know that within that patient populations the tumors may be very different to one another on genetic level and many other levels of biological differences. We knew that. What we know now is that these differences can be leveraged to choose the best treatment for each of these patients, because we may be able to predict to a certain extend whether one particular tumor is more likely or less likely to respond to one specific drug.
00:20:26:22 - 00:20:58:02
Joaquin Mateo
So, you know, until ten years ago or 50 years ago, we didn't have that many drugs to treat advanced prostate cancer. So in fairness, there was not that much research about how to choose one treatment or another because there was nothing to choose from. Right? But as we have developed more drugs that can slow down or even make the prostate cancer regress, advances in stages, there is more and more interest in understanding which biomarkers, which biological measures can help us select the best treatment for each individual patient.
00:20:58:08 - 00:21:17:18
Abigail Acton
Okay, that's fascinating. Well, Harald’s project was considering the molecular signature of the tumor itself, and in an earlier episode of CORDIScovery we considered the interplay between bacteria in the microbiome and response to chemotherapy, Joaquin tell us about the additional complexity of genetic differences between patients and how that impacts on treatment.
00:21:17:20 - 00:21:48:00
Joaquin Mateo
So we know that the prostate cancer is primarily driven by the male hormones, the androgens and almost all prostate cancers are somehow sensitive to manipulating the androgen pathway in the body. However, beyond that, there are other pathways that help the cancer cells survive that may be different from one patient to another, and some of them may be suitable for therapeutic targeting.
00:21:48:02 - 00:22:15:21
Joaquin Mateo
It is true that when we conduct research on what we call precision oncology and identifying biomarkers, many times we diagnose one gene or one protein and then see how it changes the sensitivity of the tumor. But it is true that the biological pathways in a tumor are interconnected, and the overall complexity of cancer is much higher than just targeting one protein.
00:22:15:23 - 00:22:30:19
Joaquin Mateo
So part of this study and many others that are out in the field and trying to understand how one same genetic alteration or a gene mutation may have different effects when it comes to sensitizing to attract, depending on the background, where they occur.
00:22:30:21 - 00:22:45:22
Abigail Acton
Okay. that's great. So you were looking I think the presence or the absence of a particular gene known as the ATM gene, we don't need to go into into more detail about the name. But what was so interesting about the ATM gene, what were you considering there?
00:22:45:24 - 00:23:09:16
Joaquin Mateo
So for the last ten years, I've been working in testing a family of drugs called PARP inhibitors that were already approved before in certain forms of ovarian and breast cancer. And we actually found out that they were working in certain prostate cancer patients. These prostate cancer patients were the ones that had mutations in a series of genes, one of them being this ATM gene.
00:23:09:18 - 00:23:36:13
Joaquin Mateo
What we realize when conducting clinical trials is that despite all these genes have very similar functions depending on which one was lost, the response of the tumor was very different and ATM was very puzzling because we really had a situation where some patients with these mutations, did very, very well on the treatment and some other patients didn't benefit at all.
00:23:36:15 - 00:23:49:16
Joaquin Mateo
So we wanted to go back to the laboratory and understand what does this ATM gene does for prostate cancer and actually whether it's a truly sensitizing biomarker for these drugs.
00:23:49:18 - 00:23:54:18
Abigail Acton
Ten years is a long time. Do you have some findings for us? How does how is the work going?
00:23:54:24 - 00:24:02:05
Joaquin Mateo
Yeah, actually, we've been working for a bit more than ten years on developing the drugs. These drugs are now approved and available for prostate cancer patients.
00:24:02:10 - 00:24:05:21
Abigail Acton
Fantastic. You have the drugs past the approval process, correct?
00:24:05:21 - 00:24:31:16
Joaquin Mateo
They were approved in 2020, but is still there has been a lot of controversy into which are the patients who should get the drug, because I was always saying, depending on the genetic background of the patient, the response may be more or less important for the patient or short lasting or lasting. Right? So then in the last few years, we have been looking at the impact of this ATM gene in laboratory models of prostate cancer.
00:24:31:18 - 00:24:45:06
Joaquin Mateo
We have been trying to delete these gene from cancer cells in the laboratory to see how indifferent tumors, the loss of this gene may infer different levels of sensitization to these facts.
00:24:45:09 - 00:24:52:05
Abigail Acton
Right. And data coming out. Are you establishing what that looks like, what the loss is showing?
00:24:52:09 - 00:25:15:00
Joaquin Mateo
Yes. So we published the findings of this study in 2021. One of the things that we realized is that with these ATM proteins loss, there is another backup protein in the cancer cells that takes over, and sometimes that's enough for the cancer to grow again. With that, we actually went into testing another drug that is targeting this back up pathway.
00:25:15:00 - 00:25:45:13
Joaquin Mateo
And we realized that for the patient with this mutation in particular in the ATM gene, combining the two drugs together was much better than just using one or the other. And sorry I said for patients, but actually we demonstrated that in laboratory models, we are now trying to do subsequent clinical trial testing in patients. The combination of these two drugs, although I have to say it's a bit challenging because both drugs, because they are so similar in the proteins that they target, they also have similar side effects.
00:25:45:15 - 00:25:51:02
Joaquin Mateo
So we are trying to see how to combine them in a manner that is safe for patients.
00:25:51:02 - 00:26:06:15
Abigail Acton
Right. So that's the next stage. Fascinating. That's obviously brilliant. So you've worked out the mechanism behind it. You've realized that the cancer gets around it by providing a different pathway and now you're targeting that secondary pathway. I think that's fabulous. Really, really great. Super. Does anyone have any questions for Joaquin. Yes. Harald.
00:26:06:17 - 00:26:20:01
Harald Mischak
Well, maybe one question. Did you have similar experience that it gets extremely difficult to test drugs in patients in the end? So what are your experience with talking to the regulators?
00:26:20:03 - 00:26:50:08
Joaquin Mateo
Well, that's a very long answer probably. But yes, I mean, going into clinical trials is very challenging phase of developing a biomarker drug. And one of the main issues for developing trials in the manner we wanted to investigate is that, you know, running a clinical trial is hard enough if you have to prospectively find genetic biomarkers for tumors.
00:26:50:14 - 00:27:13:21
Joaquin Mateo
It makes it even more challenging because you have to first identify those patients who may be candidates for the testing of the drug and then conduct the trial. Right. And that, you know, ends up having a layer of complexity. In general, I think that is much more difficult in our current regulatory framework in Europe to run trials to validate biomarkers than just to test the drug.
00:27:13:23 - 00:27:54:15
Joaquin Mateo
I think we have a very good setup for running clinical trials of new drugs in Europe and testing if they work or if they don't. But when it comes to linking the effect of a drug to a specific biomarker, the testing and the process of generating the sufficient evidence for approval is it's more challenging. And I think that we are also now going through a phase in Europe with the approval of the new in vitro diagnostic population, what we call the IBDR regulation, that it is making it more challenging for a good reason, right, to ensure the level of stringency in the test of the biomarker that every time that you test for
00:27:54:17 - 00:28:06:06
Joaquin Mateo
a biomarker, you only get the exact result and accurate results for that biomarker. But it is also true that it is difficult thing a bit the way we conduct biomarkers, clinical trials.
00:28:06:08 - 00:28:27:04
Abigail Acton
Thank you very, very much. I'm very, very grateful to you all because this was a technical subject and I think you've all explained it beautifully. It's been very transparent and very clear, and I'm grateful, more so grateful for all the hard work that you're all individually doing, and particularly in the face of the challenges that you're given and Joaquin and Harald just been talking about which on top of all the hard work, must after a while get a bit tiring.
00:28:27:04 - 00:28:31:18
Abigail Acton
So thank you for sticking with it much. Much appreciate it. Thank you very much.
00:28:31:20 - 00:28:34:20
ALL
Thank you. And thank you for listening.
00:28:35:15 - 00:28:38:07
Joaquin Mateo
Thank you for the interest Abigail.
00:28:38:09 - 00:28:43:03
Abigail Acton
We are all very interested in this. Of course we are. Wonderful. Thank you. Bye bye.
00:28:43:24 - 00:28:47:09
ALL
Bye bye bye.
00:28:47:11 - 00:29:10:17
Abigail Acton
If you've enjoyed this episode of CORDIScovery follow us on Spotify and Apple Podcasts and check out the podcast home page on the cordis website. Subscribe to make sure the hottest research and EU funded science isn't passing you by. And if you're enjoying listening, why not spread the word? We've talked about skin patches applied to detect TB and how access to new food sources shaped prehistoric cultures.
00:29:10:19 - 00:29:32:15
Abigail Acton
It our last 37 episodes. There'll be something there to tweak your curiosity. Perhaps you want to know what other EU funded projects are doing in the field of cancer research. The Cordis website will give you an insight into the results of projects funded by Horizon 2020 and Horizon Europe that are working in this area. Take a look at our pack of projects called Frontier Research for Cancer.
00:29:32:17 - 00:29:53:17
Abigail Acton
The website has articles and interviews that explore the results of research being conducted in a very broad range of domains and subjects from voles to volcanoes. There's something there for you. Maybe you're involved in a project or would like to apply for funding. Take a look at what others are doing in your domain. So come and check out the research that's revealing what makes our world tick.
00:29:53:19 - 00:30:01:14
Abigail Acton
We're always happy to hear from you. Drop us a line. Editorial at Cordis dot Europa dot EU. Until next time.
This is an AI transcription.
00:00:10:05 - 00:00:16:06
Abigail Acton
This is CORDIScovery.
00:00:16:08 - 00:00:41:17
Abigail Acton
Hello and welcome to this episode of CORDIScovery with me Abigail. Acton. Things are moving in the world of prostate cancer treatment. Findings just announced from the University of Oxford show that a special type of fluorescent dye might help surgeons find areas of cancerous tissue not picked up by the naked eye or other clinical methods. A new dimension in precision surgery is how it's been described by Professor Freddy Hamdy, the lead researcher.
00:00:41:19 - 00:01:07:01
Abigail Acton
Meanwhile, a new cheap and simple testing method using saliva could help catch the disease earlier by identifying the genetic factors which make men more likely to develop the condition. A leap forward in diagnostics and in treatment would be very welcome. Prostate cancer is the second most frequent malignancy in men. In 2020 alone, around one and a half million new cases and almost half a million deaths were registered worldwide.
00:01:07:03 - 00:01:17:13
Abigail Acton
The chances of survival depend on the timing of the diagnosis. Almost half of those diagnosed will survive their prostate cancer for five years or more if it is caught at an early stage.
00:01:19:02 - 00:01:41:17
Abigail Acton
Here to talk us through about some of the latest innovations brought about through the support of EU science research funding are Jan Tkac, the founder and chief scientific officer at Glycanostics in Slovakia. The company has developed an innovative diagnostic test for cancer based on novel biomarkers. Jan is also keen to explore how different sports relate to levels of endorphin release. Hello Jan.
00:01:41:19 - 00:01:43:21
Jan Tkac
Hello. Thank you very much for the invitation.
00:01:43:23 - 00:02:00:15
Abigail Acton
Lovely to have you here. Harald Mischak is the scientific officer at Mosaiques Diagnostics and Therapeutics AG Germany. He is focused on understanding the underlying molecular structures of certain types of cancers to identify the most appropriate therapeutic targets and drugs. Welcome.
00:02:00:17 - 00:02:02:13
Harald Mischak
Hello. Nice to be here.
00:02:02:15 - 00:02:20:05
Abigail Acton
Excellent. Joaquin Mateo, who is group leader at the Translational Research Group in Prostate Cancer at the Vall d’Hebron Institute of Oncology in Barcelona. He is also medical oncologist at the Aldebaran University Hospital. Joaquim is especially interested in the development of novel forms of precision medicine. Hello, Joaquin.
00:02:20:07 - 00:02:22:07
Joaquin Mateo
Hello Abigal and to everyone listening.
00:02:22:11 - 00:02:35:22
Abigail Acton
Jan, I'm going to start with you, if I may ask. ProSCAN developed an innovative glycan based early diagnostic method for prostate cancer. So can you explain what Glycans are and why are they interesting at the scientific community at the moment.
00:02:35:24 - 00:03:04:11
Jan Tkac
Thank you very much. So glycans are complex carbohydrates attached to proteins or lipids and actually glycans are present on every single cell in our body. And actually it's estimated that up to 70% of all proteins in our body are glycans oscillated. So glycans are able to provide really very useful information about physiological status of the cell. So this is one way how glycans can be used.
00:03:04:13 - 00:03:19:15
Jan Tkac
And the other one is the fact that glycans can also provide information about a development of some diseases or progression of some diseases, including cancer. And actually, this is why we are using glycans as cancer biomarkers.
00:03:19:17 - 00:03:32:04
Abigail Acton
Okay. All right. They give an accurate picture of the status of what's going on. So the ProSCAN project was hosted by your firm Glycanostics. So what's novel about your approach? Because I know scientists are interested in Glycans. What are you doing differently?
00:03:32:06 - 00:04:09:04
Jan Tkac
Okay, so actually what we are doing, we are looking at a specific glycan on specific proteins. For example, in case we would like to diagnose prostate cancer, we are looking on the differences in the glycan composition on one protein in our case its PSA, its prostate specific antigen. So how does it work? So actually, we are working in serum samples, a very complex sample containing hundreds of different proteins or glycoproteins and DNA and other molecules.
00:04:09:06 - 00:04:37:17
Jan Tkac
And actually we're using magnetic particles modified by antibodies. And actually those antibodies are able to selectively interact only with PSA molecule in this complex sample. So then these PSA molecules actually also attach to magnetic particles. Then we are using really small magnets for separation of magnetic particles and everything is washed away. And in the final step, we are using other proteins collecting.
00:04:37:20 - 00:05:06:18
Jan Tkac
And those like these are able to selectively interact with some glycan structures. And actually we are using information about differences in glycan structure for diagnosing of many diseases. So on one side we are using PSA, which is tissue specific, and on the other side we are using analysis of glycans, which are cancer specific. So by combining, we can then accurately diagnose, for example, prostate cancer.
00:05:06:20 - 00:05:23:13
Abigail Acton
Okay, this is fantastic. So basically the magnetic particles attached to the blood cancer you're interested in, and you can extract those simply by extracting the magnetic particles and they follow. That's fabulous. And is it a complex test to run? Do you have to use new equipment, specialist laboratories or?
00:05:23:16 - 00:05:52:24
Jan Tkac
No, no, actually, it's very simple. So it works in a laser format. It's very complicated named. So it's enzyme linked immunosorbent assay. But actually, this assay is very, very simple. So it runs only using ordinary equipment. We call it a laser reader. Actually, this reader is in many different laboratories worldwide, and actually it's also in clinical laboratories. So there is no need to use some special infrastructure.
00:05:53:01 - 00:06:14:11
Jan Tkac
What is really needed? It's to use only, only a laser reader, and they actually do it. So using magnetic beads, it's very, very simple. So magnetic beads allows us to work with, for example, PSA protein attached to magnetic beads. We don't need, for example, to release PSA from the magnetic beads and then to analyze this PSA separately.
00:06:14:14 - 00:06:31:22
Jan Tkac
Everything can be done on the surface of magnetic beads. So assay is very simple. It can be done in short time. And also, we can then use really small amount of our sample. For example, few drops of blood serum is really sufficient for the analysis.
00:06:32:01 - 00:06:46:08
Abigail Acton
Yes, obviously. I mean one of the problems with cancer generally, but with prostate cancer is the necessity for biopsies which can be, you know, tricky to achieve. They're expensive and there can be side effects and so on. And I believe that your technique greatly reduce the need for that sort of tissue.
00:06:46:10 - 00:07:12:24
Jan Tkac
So actually we are working with serum samples. So this means that our approach is early stage cancer diagnostics. And this is really needed because, for example, an urologist needs to manage patient properly, for example, to suggest should this patient needs to undergo a biopsy or no. And actually our test can provide second opinion to guide urologist.
00:07:12:24 - 00:07:30:23
Jan Tkac
If patient needs to undergo a biopsy. And actually, in last clinical validation study, when we showed that our test is the best path from all surgical tests which are currently available on the market, and actually we could significantly reduce number of biopsies using our test.
00:07:31:00 - 00:07:49:24
Abigail Acton
Excellent, which is stress and money and time, which is obviously crucial and in the case of diagnosis for cancer. And how is the system working in practice? So is your system of analysis actually in place in certain health centers and environments in hospitals? Or when could people expect to be able to benefit from this innovation?
00:07:50:01 - 00:08:16:21
Jan Tkac
So actually, when is in a laser format, and it's very easy to transfer this technology also on highly automatic machines of industry leaders. And actually in our case, since we are using magnetic particles in our assay this transfer is more convenient for big diagnostic or pharma companies at a later stage, because all those early automatic machines actually involve the use of magnetic particles.
00:08:17:02 - 00:08:36:09
Jan Tkac
So this is going to be beneficial in our case. And currently we are in Slovakia running testing. So actually we have some agreement with urologists in Slovakia so patients can pay for this kind of service and urologists can provide really very useful information on how to manage the patient.
00:08:36:11 - 00:08:40:09
Abigail Acton
Okay, that sounds wonderful. You must be very proud of all the work that you've achieved so far.
00:08:40:11 - 00:08:52:06
Jan Tkac
Yeah, it was really hard work. Yes, but it's good that this test can be actually used. So we started in Slovakia and we would like to extend use of this test in other countries as well.
00:08:52:07 - 00:09:01:02
Abigail Acton
Yeah, of course. Absolutely. And how long did it take you to develop this system? Because it must have been a long time in the pipeline.
00:09:01:07 - 00:09:30:01
Jan Tkac
Yes, Actually, it started with an ERC grant. It was in 2012. Then in 2017, we established a company, but then it took quite significant time, for example, to get finances and an investment and fully develop the product. So from the start of the company, it's almost seven years now. So it was quite a long journey. But yeah, it was a really nice experience.
00:09:30:03 - 00:09:50:17
Abigail Acton
But now finally you actually going to see the benefit when it comes out. I think that's wonderful. Thank you so much. That was a very interesting explanation and beautifully set up. Thank you for that. I'm going to turn to Harald please. Harald as drugs act on a molecular level. The molecular differences between patients means that while a drug can benefit some, it might not be effective for all.
00:09:50:19 - 00:10:07:02
Abigail Acton
PCaProTreat wanted to unravel this for better diagnosis and treatment. So Harald, like Jan your project, also considered less invasive ways of diagnosis in this case noninvasive urinary biomarkers that enable early detection of prostate cancer. Can you tell us more about this form of analysis first?
00:10:07:08 - 00:10:37:01
Harald Mischak
Yeah, that was developed out of a project to basically identify different diseases based on urinary peptides. We have to consider that in general, all smaller proteins and peptides are present in the engineering, so whatever is in circulation will be filtered, they'll be in urine and urine has two main advantage from a technical point of view that it's quite stable, that urine has been stored in the bladder for several hours at 37 degrees.
00:10:37:03 - 00:10:44:12
Harald Mischak
So whatever we can detect in there is stable and can therefore also be shaped among all sampling issues.
00:10:44:14 - 00:10:45:07
Abigail Acton
Okay.
00:10:45:09 - 00:10:59:16
Harald Mischak
It works quite well for kidney, cardiovascular disease. And then we also played it for prostate cancer, among other cancers, and found there are many specific proteins and peptides in urine that indicate the presence of cancer.
00:10:59:22 - 00:11:09:12
Abigail Acton
Okay. So I know that your project gathered molecular proteomics data from thousands of prostate cancer patients. So what did that enable your team to do?
00:11:09:14 - 00:11:37:21
Harald Mischak
To identify which proteins and peptides are significantly associated with cancer. As with prostate cancer in this way, which proteins are indicative of aggressive cancer, you may consider that most prostate cancer patients do not die from the counts but with the cancer. That is a big issue. So in most cases I would also argue it would be better for the patients not even knowing that they have cancer if they can't do anything anyway.
00:11:37:23 - 00:12:06:04
Harald Mischak
Anyway, these proteins in the end are to some degree also responsible for the cancer. So therefore they form. If you want to say that the molecular basis of the cancer, knowing these proteins means I know where exactly to interfere. And using all this information theoretically on all of the properties of the changed, I can predict which molecules, drugs or whatever I can use to revert these changes, basically.
00:12:06:06 - 00:12:16:16
Abigail Acton
Okay. So it's like a comprehensive profile of the particular cancer that the patient has gives you all the like a real thorough painting, like a portrait of a particular cancer.
00:12:16:18 - 00:12:32:12
Harald Mischak
Yes. Also, I can't say it's not it's not a cancer sort of speaking of, cancer is quite heterogeneous. And this micro heterogeneity in cancer really is the big problem. But typically, cancer cannot be cured easily.
00:12:32:14 - 00:12:42:06
Abigail Acton
Right. And I know that your project was really looking at a multi-omics approach. Can you explain what a multi-omics approach is? And I believe it's quite innovative.
00:12:42:08 - 00:13:11:09
Harald Mischak
There are different so-called omics techniques, proteomics, investigating proteins, transcriptome omics investigate the DNA transcripts that are called the proteins, genomics investigating the DNA and so on. All of these have in common that they investigate thousands of different molecules and some of these are changed in disease. And together they of course are able to let's take even more comprehensive picture of the specific disease.
00:13:11:15 - 00:13:22:14
Abigail Acton
Right. Okay. So it's like a holistic approach. And then, of course, you end up with a huge amount of data. So, there has been computational work on in your project as well.
00:13:22:16 - 00:13:49:24
Harald Mischak
Yes, there is plenty of computational work involved. Obviously plenty of experts, and certainly the work has profited a lot from collaboration with multiple different scientists in the field of, let's say, bioinformatics, systems, medicine and so on. Where I come from as well. We also have benefited basically from our experience in molecular diagnostics where we run into the same problem.
00:13:50:01 - 00:14:09:20
Abigail Acton
Right. Well, I'd like to talk about the molecular diagnostics now actually. So I mean, as we've just said, cancer is a very complex structures notoriously hard to treat. So I knew that one of the things you were interested in was reverse engineering, what was going on actually to cause the cancer growth. Could you tell me a little bit more about what you meant by reverse engineering in this concept?
00:14:09:22 - 00:14:46:02
Harald Mischak
In principle, as I said, the cancer, basically any kind of disease is determined on the molecular level. You have specific molecular changes associated with disease. Some of these are in fact decisive and decide on the direction of disease. If you know these changes, you can use small molecular weight compounds or also antisense RNA, anti proteins, whatever. To revert this change, you bring the molecular signature of the cell or the accumulation of cells back to where it was before.
00:14:46:04 - 00:15:13:17
Harald Mischak
And this would imply that the disease in this case, the tumor, is also reported. This is what you would call the reverse engineering. We know about a lot of drugs and compounds, how they interfere or how they change expression of certain proteins. And then we just overlay these different patterns to predict which of the drugs may be most useful in a specific type of cancer or for a specific patient.
00:15:13:17 - 00:15:32:14
Abigail Acton
Thank you very much. That's a very clear explanation. I'm appreciating both of these fantastic explanations. So, building on these findings, you were looking for potential drug candidates. So where are you up to with this? What what did all of this analysis and complex computer work as well show you? Where does it leave us?
00:15:32:16 - 00:16:00:08
Harald Mischak
Well, now we have seven candidates, drug candidates shortlisted and these we now need to investigate in more detail. We need to demonstrate whether where we know from some of them by now that they in fact revert to tumor phenotype in cell lines, in vitro or as in the tissue culture. This is where it stops because the approach beyond is quite expensive and there is a huge regulatory burden.
00:16:00:10 - 00:16:05:04
Harald Mischak
And here, unfortunately, I have to say we have to try to find funding.
00:16:05:06 - 00:16:18:03
Abigail Acton
Yeah, we must be quite frustrating when, you know, you're sitting on something that is actually potentially really, you know, going to save lives and turn situations around and presumably not just for prostate cancer, but perhaps could be applied to other cancers as well.
00:16:18:03 - 00:16:24:09
Harald Mischak
No, you're right. It is frustrating. We have to find funding from private venture capital companies.
00:16:24:23 - 00:16:25:14
Abigail Acton
00:16:25:16 - 00:16:35:24
Harald Mischak
That’s what we are doing and all the patient organizations now support us and try to find the funding because in the end of course, the patients would benefit from an improved drug.
00:16:36:03 - 00:16:44:24
Abigail Acton
You know, potentially life saving. Absolutely. Okay. Thank you so much for explaining that so clearly. Does anyone have any comments? Yes, please. Joaquin.
00:16:45:01 - 00:17:03:10
Joaquin Mateo
I want to ask my colleagues. I mean, first of all, congratulations for your work is really amazing. But I want to ask Harald if beyond the applications for diagnostics, have you ever tested whether this urine test could actually detect a relapse of the disease on a patient that has already had surgery for their prostate tumor?
00:17:03:12 - 00:17:25:24
Harald Mischak
We have not investigated this in detail, I would assume, yes. We tested this in a slightly different context in bladder cancer where the tumor is removed. But as you know, frequently these patients develop novel or relapse of the tumor and they are be tested. And we found that, in fact, yes, we can detect the relapse of the tumor.
00:17:26:05 - 00:17:42:19
Harald Mischak
Of course, it's a matter of size also. So I would say that you cannot. It's difficult to detect the few tumor cells, but once the tumor reaches a certain size of maybe 1 to 2 millimeters, quite easy to detect using this technology.
00:17:42:21 - 00:17:58:20
Abigail Acton
Fantastic. That's excellent. That's really, really good. Like almost a thermometer, sort of keeping an eye without being invasive and again presumably as you said the urine stores well, it's easy to access. It's easy to use. Brilliant. Thank you.
00:17:58:22 - 00:18:11:07
Harald Mischak
The one advantage that these have pointed out as well is that we now have data from close to 90,000 patients with different diseases and controls. So this helps to be quite certain about the statistics behind it.
00:18:11:09 - 00:18:20:18
Abigail Acton
That's an awful lot of patients. Gosh, were they all taken? What database is this? Is this some sort of a collective database?
00:18:20:19 - 00:18:27:06
Harald Mischak
Yes, that’s a collection. We were involved in many European projects so is a collection of all of these samples and data.
00:18:27:06 - 00:18:50:01
Abigail Acton
Okay. Fabulous. I mean, that's very rich resource. Very useful. Super. Okay. Thank you so much. Joaquin I'm going to turn to you now. The AR-DDR project looked at the exchange between two key pathways involved in prostate cancer development. So you're interested in treatment. We've been looking at diagnostics now returning to treatment. You want to optimize precise therapeutic options.
00:18:50:03 - 00:18:58:15
Abigail Acton
So when you say prostate cancer, we think of one single disease. But as Jan was explaining as well, that's not quite accurate. Joaquin, can you tell us more about the condition, please?
00:18:58:17 - 00:19:21:09
Joaquin Mateo
Yes, I think that we have just added from our colleagues two brilliant studies on how to better diagnose and treat initial stages of prostate cancer. Certainly in most prostate cancer are diagnosed at the time. What that is confined to the proceeding can be cured, but we know that certain patients develop upfront an advanced prostate cancer condition.
00:19:21:09 - 00:19:45:09
Joaquin Mateo
So the cancer has spread outside the prostate to other organs. We know very well now that this what we call localized prostate cancer and what we call metastatic or advanced prostate cancer are two different biological entities, and that the molecular features of their localized or advanced cases are very different. So that's a difference.
00:19:45:09 - 00:20:26:20
Joaquin Mateo
But when we go to the field where I work on and maybe I might be biased because I work on the minority of prostate cancers that are very aggressive and had spread outside the organs, we still know that within that patient populations the tumors may be very different to one another on genetic level and many other levels of biological differences. We knew that. What we know now is that these differences can be leveraged to choose the best treatment for each of these patients, because we may be able to predict to a certain extend whether one particular tumor is more likely or less likely to respond to one specific drug.
00:20:26:22 - 00:20:58:02
Joaquin Mateo
So, you know, until ten years ago or 50 years ago, we didn't have that many drugs to treat advanced prostate cancer. So in fairness, there was not that much research about how to choose one treatment or another because there was nothing to choose from. Right? But as we have developed more drugs that can slow down or even make the prostate cancer regress, advances in stages, there is more and more interest in understanding which biomarkers, which biological measures can help us select the best treatment for each individual patient.
00:20:58:08 - 00:21:17:18
Abigail Acton
Okay, that's fascinating. Well, Harald’s project was considering the molecular signature of the tumor itself, and in an earlier episode of CORDIScovery we considered the interplay between bacteria in the microbiome and response to chemotherapy, Joaquin tell us about the additional complexity of genetic differences between patients and how that impacts on treatment.
00:21:17:20 - 00:21:48:00
Joaquin Mateo
So we know that the prostate cancer is primarily driven by the male hormones, the androgens and almost all prostate cancers are somehow sensitive to manipulating the androgen pathway in the body. However, beyond that, there are other pathways that help the cancer cells survive that may be different from one patient to another, and some of them may be suitable for therapeutic targeting.
00:21:48:02 - 00:22:15:21
Joaquin Mateo
It is true that when we conduct research on what we call precision oncology and identifying biomarkers, many times we diagnose one gene or one protein and then see how it changes the sensitivity of the tumor. But it is true that the biological pathways in a tumor are interconnected, and the overall complexity of cancer is much higher than just targeting one protein.
00:22:15:23 - 00:22:30:19
Joaquin Mateo
So part of this study and many others that are out in the field and trying to understand how one same genetic alteration or a gene mutation may have different effects when it comes to sensitizing to attract, depending on the background, where they occur.
00:22:30:21 - 00:22:45:22
Abigail Acton
Okay. that's great. So you were looking I think the presence or the absence of a particular gene known as the ATM gene, we don't need to go into into more detail about the name. But what was so interesting about the ATM gene, what were you considering there?
00:22:45:24 - 00:23:09:16
Joaquin Mateo
So for the last ten years, I've been working in testing a family of drugs called PARP inhibitors that were already approved before in certain forms of ovarian and breast cancer. And we actually found out that they were working in certain prostate cancer patients. These prostate cancer patients were the ones that had mutations in a series of genes, one of them being this ATM gene.
00:23:09:18 - 00:23:36:13
Joaquin Mateo
What we realize when conducting clinical trials is that despite all these genes have very similar functions depending on which one was lost, the response of the tumor was very different and ATM was very puzzling because we really had a situation where some patients with these mutations, did very, very well on the treatment and some other patients didn't benefit at all.
00:23:36:15 - 00:23:49:16
Joaquin Mateo
So we wanted to go back to the laboratory and understand what does this ATM gene does for prostate cancer and actually whether it's a truly sensitizing biomarker for these drugs.
00:23:49:18 - 00:23:54:18
Abigail Acton
Ten years is a long time. Do you have some findings for us? How does how is the work going?
00:23:54:24 - 00:24:02:05
Joaquin Mateo
Yeah, actually, we've been working for a bit more than ten years on developing the drugs. These drugs are now approved and available for prostate cancer patients.
00:24:02:10 - 00:24:05:21
Abigail Acton
Fantastic. You have the drugs past the approval process, correct?
00:24:05:21 - 00:24:31:16
Joaquin Mateo
They were approved in 2020, but is still there has been a lot of controversy into which are the patients who should get the drug, because I was always saying, depending on the genetic background of the patient, the response may be more or less important for the patient or short lasting or lasting. Right? So then in the last few years, we have been looking at the impact of this ATM gene in laboratory models of prostate cancer.
00:24:31:18 - 00:24:45:06
Joaquin Mateo
We have been trying to delete these gene from cancer cells in the laboratory to see how indifferent tumors, the loss of this gene may infer different levels of sensitization to these facts.
00:24:45:09 - 00:24:52:05
Abigail Acton
Right. And data coming out. Are you establishing what that looks like, what the loss is showing?
00:24:52:09 - 00:25:15:00
Joaquin Mateo
Yes. So we published the findings of this study in 2021. One of the things that we realized is that with these ATM proteins loss, there is another backup protein in the cancer cells that takes over, and sometimes that's enough for the cancer to grow again. With that, we actually went into testing another drug that is targeting this back up pathway.
00:25:15:00 - 00:25:45:13
Joaquin Mateo
And we realized that for the patient with this mutation in particular in the ATM gene, combining the two drugs together was much better than just using one or the other. And sorry I said for patients, but actually we demonstrated that in laboratory models, we are now trying to do subsequent clinical trial testing in patients. The combination of these two drugs, although I have to say it's a bit challenging because both drugs, because they are so similar in the proteins that they target, they also have similar side effects.
00:25:45:15 - 00:25:51:02
Joaquin Mateo
So we are trying to see how to combine them in a manner that is safe for patients.
00:25:51:02 - 00:26:06:15
Abigail Acton
Right. So that's the next stage. Fascinating. That's obviously brilliant. So you've worked out the mechanism behind it. You've realized that the cancer gets around it by providing a different pathway and now you're targeting that secondary pathway. I think that's fabulous. Really, really great. Super. Does anyone have any questions for Joaquin. Yes. Harald.
00:26:06:17 - 00:26:20:01
Harald Mischak
Well, maybe one question. Did you have similar experience that it gets extremely difficult to test drugs in patients in the end? So what are your experience with talking to the regulators?
00:26:20:03 - 00:26:50:08
Joaquin Mateo
Well, that's a very long answer probably. But yes, I mean, going into clinical trials is very challenging phase of developing a biomarker drug. And one of the main issues for developing trials in the manner we wanted to investigate is that, you know, running a clinical trial is hard enough if you have to prospectively find genetic biomarkers for tumors.
00:26:50:14 - 00:27:13:21
Joaquin Mateo
It makes it even more challenging because you have to first identify those patients who may be candidates for the testing of the drug and then conduct the trial. Right. And that, you know, ends up having a layer of complexity. In general, I think that is much more difficult in our current regulatory framework in Europe to run trials to validate biomarkers than just to test the drug.
00:27:13:23 - 00:27:54:15
Joaquin Mateo
I think we have a very good setup for running clinical trials of new drugs in Europe and testing if they work or if they don't. But when it comes to linking the effect of a drug to a specific biomarker, the testing and the process of generating the sufficient evidence for approval is it's more challenging. And I think that we are also now going through a phase in Europe with the approval of the new in vitro diagnostic population, what we call the IBDR regulation, that it is making it more challenging for a good reason, right, to ensure the level of stringency in the test of the biomarker that every time that you test for
00:27:54:17 - 00:28:06:06
Joaquin Mateo
a biomarker, you only get the exact result and accurate results for that biomarker. But it is also true that it is difficult thing a bit the way we conduct biomarkers, clinical trials.
00:28:06:08 - 00:28:27:04
Abigail Acton
Thank you very, very much. I'm very, very grateful to you all because this was a technical subject and I think you've all explained it beautifully. It's been very transparent and very clear, and I'm grateful, more so grateful for all the hard work that you're all individually doing, and particularly in the face of the challenges that you're given and Joaquin and Harald just been talking about which on top of all the hard work, must after a while get a bit tiring.
00:28:27:04 - 00:28:31:18
Abigail Acton
So thank you for sticking with it much. Much appreciate it. Thank you very much.
00:28:31:20 - 00:28:34:20
ALL
Thank you. And thank you for listening.
00:28:35:15 - 00:28:38:07
Joaquin Mateo
Thank you for the interest Abigail.
00:28:38:09 - 00:28:43:03
Abigail Acton
We are all very interested in this. Of course we are. Wonderful. Thank you. Bye bye.
00:28:43:24 - 00:28:47:09
ALL
Bye bye bye.
00:28:47:11 - 00:29:10:17
Abigail Acton
If you've enjoyed this episode of CORDIScovery follow us on Spotify and Apple Podcasts and check out the podcast home page on the cordis website. Subscribe to make sure the hottest research and EU funded science isn't passing you by. And if you're enjoying listening, why not spread the word? We've talked about skin patches applied to detect TB and how access to new food sources shaped prehistoric cultures.
00:29:10:19 - 00:29:32:15
Abigail Acton
It our last 37 episodes. There'll be something there to tweak your curiosity. Perhaps you want to know what other EU funded projects are doing in the field of cancer research. The Cordis website will give you an insight into the results of projects funded by Horizon 2020 and Horizon Europe that are working in this area. Take a look at our pack of projects called Frontier Research for Cancer.
00:29:32:17 - 00:29:53:17
Abigail Acton
The website has articles and interviews that explore the results of research being conducted in a very broad range of domains and subjects from voles to volcanoes. There's something there for you. Maybe you're involved in a project or would like to apply for funding. Take a look at what others are doing in your domain. So come and check out the research that's revealing what makes our world tick.
00:29:53:19 - 00:30:01:14
Abigail Acton
We're always happy to hear from you. Drop us a line. Editorial at Cordis dot Europa dot EU. Until next time.
Quicker diagnosis, individually tailored therapies
Things are moving in the world of prostate cancer treatment. Findings just announced from the University of Oxford show that a special type of fluorescent dye might help surgeons find areas of cancerous tissue not picked up by the naked eye, or other clinical methods. “A new dimension in precision surgery”, is how it has been described by Freddy Hamdy, the lead researcher. Meanwhile a new, cheap and simple testing method using saliva could help catch the disease earlier by identifying the genetic factors which make men more likely to develop the disease. A leap forward in the diagnosis and treatment would be very welcome: prostate cancer is the second most frequent malignancy in men. In 2020 alone, around one and a half million new cases and almost half a million deaths were registered worldwide. The chances of survival depend on the timing of the diagnosis: almost half those diagnosed will survive their prostate cancer for five years or more if it is caught at an early stage. Our three guests today explain how their EU-funded research is furthering that goal: Jan Tkac is the founder and chief scientific officer at Glycanostics, in Slovakia. The company has developed an innovative diagnostic test for cancer, based on novel biomarkers, partly carried out under the ProSCAN project. Jan is also keen to explore how different sports relate to the levels of endorphin release. Harald Mischak, the chief scientific officer of Mosaiques Diagnostics & Therapeutics, Germany, is focused on understanding the underlying molecular structures of certain types of cancers. His project, PCaProTreat, set out to identify the most appropriate therapeutic targets and drugs. Joaquin Mateo is group leader of the Prostate Cancer Translational Research Group at Vall d’Hebron Institute of Oncology, in Barcelona. He is especially interested in the development of novel forms of precision medicine, which he explored through the AR-DDR project.
Happy to hear from you!
If you have any feedback, we’re always happy to hear from you! Send us any comments, questions or suggestions to: editorial@cordis.europa.eu.
Keywords
ProSCAN, PCaProTreat, AR-DDR, CORDIS, prostate cancer, health, diagnosis, treatment, precision surgery, personalised treatment