1 00:00:03,290 --> 00:00:19,140 Any. I've known Vincent for many, many years, and if he recalls, I think I do as I examine these Ph.D theses in Newcastle. 2 00:00:19,140 --> 00:00:28,380 So Vincent graduated from Newcastle initially, then became a clinical training fellow. 3 00:00:28,380 --> 00:00:38,910 See our UK to do his the film. After his DPhil, he became a clinical lecturer at Newcastle 2003 and became, 4 00:00:38,910 --> 00:00:47,280 I believe, the first see our UK clinician scientist that was given to a surgeon. 5 00:00:47,280 --> 00:00:56,490 Then he joined Cambridge and became honorary consultant and has been leading a group now on prostate cancer research. 6 00:00:56,490 --> 00:01:07,470 He's got, uh, many publications to his credit, and he's got a number of very interesting projects that he has been leading. 7 00:01:07,470 --> 00:01:18,960 And his research is really very grounded, going from genetics through to having clinical applications of risk calculators that he will talk to us. 8 00:01:18,960 --> 00:01:27,780 And this is a powerful instrument, I believe, which has a lot of a lot of mileage. 9 00:01:27,780 --> 00:01:39,390 So your colleagues also the CIA, Cambridge Cancer Centre on neurological cancers and a group on translational research and the Clinical Trials Office. 10 00:01:39,390 --> 00:01:43,530 So without delaying you further, Vincent, warm welcome. 11 00:01:43,530 --> 00:01:52,530 Thank you very much for coming. Thank you, Freddie, it's a great honour to be invited because not only did you examine my Ph.D., 12 00:01:52,530 --> 00:01:57,450 you were also a senior lecturer at the time when I was a humble, asexual and didn't speak to you. 13 00:01:57,450 --> 00:02:04,140 So I think I've achieved something to get here today. So thank you very much for the kind of invite. 14 00:02:04,140 --> 00:02:10,860 And what I want to talk to you about today is actually a research journey as much as the things we've developed, 15 00:02:10,860 --> 00:02:13,620 because when I started off in this area, 16 00:02:13,620 --> 00:02:20,370 I was led very much by what I was told needs to be done and very quickly got to the point where I question what needed to be done. 17 00:02:20,370 --> 00:02:28,890 And now the question is what should we be doing? So I'll first of give you some context as to where I work and what I do. 18 00:02:28,890 --> 00:02:35,700 As you said, I started off in Newcastle and then got pulled into the Dragon's Den of Cambridge. 19 00:02:35,700 --> 00:02:38,220 And Herbie Newell, who was up in Newcastle, 20 00:02:38,220 --> 00:02:43,140 told me to be very careful when I went there because it's full of people who are you looking up to stab you in the back? 21 00:02:43,140 --> 00:02:53,360 It's not as bad as that, but actually it is a very challenging environment and you really need to know your stuff, which actually is a good thing. 22 00:02:53,360 --> 00:02:58,250 These are the organisations that I, if you like, lead and we've developed over the last five years, 23 00:02:58,250 --> 00:03:04,500 obviously, we are lucky to have a big programme of academic urology trainees and the academic urology group. 24 00:03:04,500 --> 00:03:08,390 We have set up the Cambridge Urology Translational and Clinical Trials Office, 25 00:03:08,390 --> 00:03:12,890 which is in these humble buildings up there, and we've got a fabulous team of people who work together. 26 00:03:12,890 --> 00:03:18,530 And I also happen to co-lead the CEO UK um, urological malignancies programme with Professor Eamon Maher, 27 00:03:18,530 --> 00:03:24,200 which is a very large, UK funded infrastructure for all kinds of research. 28 00:03:24,200 --> 00:03:29,360 More important than that is I'm very privileged to work together with some amazing colleagues, 29 00:03:29,360 --> 00:03:35,780 and one of the key insights that I can ever gain have ever gained and can ever impart is it is of no value to be 30 00:03:35,780 --> 00:03:43,190 personally successful because it only success makes success for you and your impact when you reach is very limited. 31 00:03:43,190 --> 00:03:51,110 Instead, we've been able to work with a whole bunch of colleagues here in academic oncology, clinical oncology to basic sciences, engineering, 32 00:03:51,110 --> 00:03:58,160 radiology, pathology and also our clinical colleagues as well all centred around an infrastructure which has been very successful. 33 00:03:58,160 --> 00:04:03,290 We've had pretty good, you know, research income and many more papers published. 34 00:04:03,290 --> 00:04:10,580 And this is the resource which I am very fortunate to work with them to be able to deliver what we do. 35 00:04:10,580 --> 00:04:14,990 We also have this. Now this is a bioethics called diamond, 36 00:04:14,990 --> 00:04:22,100 which is actually one of the most powerful ethics around to be able to do studies because we can flex it to do nearly everything. 37 00:04:22,100 --> 00:04:27,470 We have over two and a half thousand men in diamond. We have got imaging, we've got guided biopsies. 38 00:04:27,470 --> 00:04:32,720 We can get them involved in ICM trials. We can do get all your samples for all kinds of collections, 39 00:04:32,720 --> 00:04:38,720 and we've used it for a number of applications and also for redefining prognostic categories at the moment. 40 00:04:38,720 --> 00:04:46,070 This continues to recruit for bespoke studies, but is a resource which is highly annotated to answer any question we have and indeed 41 00:04:46,070 --> 00:04:52,680 allows us to actually undertake both multi-center trials and also translational research. 42 00:04:52,680 --> 00:04:59,250 We have led a number of national studies, these are just some of the ones we've just completed, working with many different sites, 43 00:04:59,250 --> 00:05:05,850 looking around neoadjuvant studies, a new device for prostate biopsies we've developed to predict prostate to or talk about. 44 00:05:05,850 --> 00:05:11,040 And the five study, which I'll explain a little bit more about, which integrates biomarkers in imaging. 45 00:05:11,040 --> 00:05:16,590 And these connexions has allowed us to explore how we take ideas generated from Cambridge and work with other centres. 46 00:05:16,590 --> 00:05:20,850 So to be clear, this is not studies that are coming from commercial companies or other bodies. 47 00:05:20,850 --> 00:05:25,130 These are things that we have actually originated. 48 00:05:25,130 --> 00:05:32,030 So I put this up to remind me of if you like, where I started, so back in the day when I was looking at my Ph.D., 49 00:05:32,030 --> 00:05:36,830 I was particularly interested in this molecule called SCEF, because that was what the lab did in Newcastle. 50 00:05:36,830 --> 00:05:42,020 They were into molecular biology and FGF signalling fabulous growth factors. 51 00:05:42,020 --> 00:05:49,730 And I quickly identified that this molecule seemed to be very important in FGF regulation and had a profound effect in altering biology. 52 00:05:49,730 --> 00:05:56,420 And this was relevant because growth factor signalling in FGF was the area of interest in prostate cancer. 53 00:05:56,420 --> 00:06:03,680 And this led to a number of publications in lots of different journals, which was really nice for the science and actually advancing knowledge base. 54 00:06:03,680 --> 00:06:11,450 But it quickly became apparent to me that I wasn't actually show where this was all heading, but it has been successful. 55 00:06:11,450 --> 00:06:16,490 This is a slide which I think I might remember from A.N. Lecture some time ago, 56 00:06:16,490 --> 00:06:24,080 and we were able to show through many publications that the FGF signalling axis was altered at multiple different levels effectively. 57 00:06:24,080 --> 00:06:31,760 If you looked at one thing that would not tell you the tale, so we showed that not only were ligands upregulated, the receptors were upregulated. 58 00:06:31,760 --> 00:06:39,530 And more importantly, there was a whole layer of regulation of these signalling pathways, which are also upregulated or downregulated. 59 00:06:39,530 --> 00:06:44,780 So in effect, if you were to design something to target this bit, these other things would compensate. 60 00:06:44,780 --> 00:06:50,510 And it actually turns out that this was a very important lesson in hindsight, because nothing sits on its own. 61 00:06:50,510 --> 00:06:54,620 And therefore we're only looking at one part of things and you forget something else and you spend lots 62 00:06:54,620 --> 00:07:00,230 and lots of money developing a drug war that you will probably fail because the tumours can adapt. 63 00:07:00,230 --> 00:07:03,350 And in fact, people can adapt funny. 64 00:07:03,350 --> 00:07:09,560 So really, at the end of all of this was this question of what was the relevance of the work that I, as a urologist, 65 00:07:09,560 --> 00:07:16,190 as a as a urological surgeon and interest in prostate cancer was achieving by doing molecular biology at this level? 66 00:07:16,190 --> 00:07:22,100 Don't get me wrong, it was important work to be done, but a value added wasn't very clear to me. 67 00:07:22,100 --> 00:07:23,660 And then there was another piece of work, 68 00:07:23,660 --> 00:07:30,890 which I did because I was trying to think along these lines as to what is it we were actually doing in the labs and what we were looking for, 69 00:07:30,890 --> 00:07:39,440 particularly around biomarkers. Because as a urologist, I was entirely focussed on radical prostatectomy, surgical removal of the prostate gland. 70 00:07:39,440 --> 00:07:44,640 And that was what we were looking for. Biomarkers relapse after that. So this was a piece of work which.