S3.20 The Future of Cancer: How Genomics is Transforming Research and Treatment for All
Kat: Hello, and welcome to Genetics Unzipped - the Genetics Society podcast, with me, Dr Kat Arney. In this episode, sponsored by Thermo Fisher Scientific, we’re taking a look at how genomic technologies are transforming cancer care - now and in the future, and the importance of making sure that these advances are available to all.
Before we start, if you’d like to know more about where cancer came from, where it’s going, and how we might beat it, my new book, Rebel Cell: Cancer, Evolution and the Science of Life is out now in the UK and you can find all the links to buy it from your favourite retailer - as well as signed book plate stickers and limited edition signed hardbacks - at rebelcellbook.com.
Congratulations to Simon Wood who’s the winner of our prize draw for a signed copy of the UK version. We’ll be running a draw for the US version soon - unfortunately the US print run is an indirect victim of COVID and has been delayed, but hopefully it’ll be arriving towards the end of October so listen out for that. And of course you can still pre-order it now from rebelcellbook.com.
From Mutations to Moonshots
In recent years we’ve seen huge advances in the way that we think about cancer - and the way that we treat it. Rather than putting patients into broad ‘buckets’ - bowel cancer, breast cancer and so on - we’re moving towards a more sophisticated view of each individual person’s disease, driven by increasing knowledge of the genetic and molecular faults that underpin their unique disease, and selecting more personalised treatments that should have a better chance of working.
One of the best qualified people to talk about this new way of thinking about cancer - known as precision medicine - is Greg Simon, past president of the Biden Cancer Initiative and former executive director of the White House Cancer Moonshot Task Force under President Obama and vice-president Biden.
I was lucky enough to sit down with him at the Manova Global Health Summit in Minneapolis last year for a chat about where we’ve come in terms of precision medicine for cancer and where we’re heading in the future.
Greg: Well, you know, precision medicine has two parts - being precise and being medicine - and often we know one but not the other. So we have lots of medicines, but we're not quite sure where to target them because we haven't discovered the mutation of the gene that makes precision possible with those medicines. So we're learning a lot about people through genetic testing, through wearables, through interviews and behaviour, everything. But that doesn't mean that we know what to do for them. It's kind of like quantum physics, where when you opened Schrodinger's cat in the box, maybe it's alive, maybe it's dead, but you don't know until you open the box. We're in the same way - if we know the specific conditions with people, we always know what to do about it. And if we have a medicine that we think works for people, we still don't know where to target it. We're at the beginning of that, we're not at the end. We're at the beginning.
Kat: There has been a huge amount of excitement in recent years about smart drugs, about genetically targeted drugs, about people getting their tumour genome sequenced. How much of this is actual reality on the ground? The reality-based medicine, because looking at the headlines you'd think, right, that's it, we've got it, everyone gets their tumour analyzed and we know exactly what drugs to give everybody. What is the reality?
Greg: Well, it's kind of like the reality with the early fax machines and the early internet. If you wait until everybody's on it, it's too late. But if you're the first one with the fax machine, who are you going to call? Right? So yes, everyone with cancer should get sequenced, period. Why? Is it going to necessarily help them? No, but we have got to start gathering that level of information across the population. We will see things in a million people you can't see in a thousand and we'll see things in a hundred million people you can't see in a million, but the only way to see any of it is to start sequencing, tumours, sequencing, healthy people, taking early blood detection tests, all sorts of things that we can do to monitor the development of disease. And if we're lucky enough to catch certain cancers early, we can also see what makes them deadly later and try to prevent that in the general population. It is not true that we have an answer for every question, but it is true that we need to keep asking those questions because we'll never get to the true precision medicine reality if we don't do a lot of things that might look useless right now, but they're going to be highly valuable later.
Kat: One of the things I find very interesting is the assumption almost that precision medicine will mean one magic bullet we'll know your cancer. It'll be one drug, that'll be it. But now we're looking at examples of some of these very targeted drugs and just seeing that they work for a little bit, and then the cancers evolve resistance and then they're back, and then you're really in trouble. So how do we try and square that circle of wanting to use this genetic knowledge to develop very precise drugs, and then the problem of cancer being an evolutionary beast and just evolving its way around.
Greg: Right. The biggest important thing about cancer with the exception of a few virus related cancers is that it starts as you, it's not an invader. It has the ability to use all of you to keep itself alive. And if you were watching a movie, cancer's always the hero of the movie, because it doesn't want to die.
Kat: And it never bloody dies.
Greg: It never bloody dies. So if you look at the world from the point of view of the cancer cell, everything's lined up for it to survive, adapt, evolve, escape, because it knows more about your biology than you do - or medicine does. Modern medicine knows less about our cancer biology than cancer cells do, because cancer cells know how to hide, how to turn off the police, how to turn off the detection system, turn on the sprinkler system, spread around... It's brilliant. And we're just now catching up to it.
Kat: So what is needed in terms of research to actually start understanding those processes of evolution, the way that cancer is tapping into those very deep genetic networks that are in there?
Greg: Well, you raise a very complex point. So there are two parts to that. Number one, there are people who understand a lot about cells and a lot about cancer. That's sort of the job of the National Institutes of Health, to study biology. It's not their mission to cure anything. So if we wait until we understand everything about cancer, we won't cure anything. We know enough to take chances, to try to save people from the cancers that we know how to deal with. What we don't know, we can't let stop us from doing the things that we think we should do. And it will be decades, if ever, that we understand all there is to know about cancer. But we know enough that we can start taking chances, and those chances often work out into new therapies and new treatments.
Kat: Where do you think the most exciting directions are coming from? We've seen the revolution in immunotherapy and a Nobel prize for the discovers of those inhibitors that unleash the immune system onto cancer. But where else maybe should we be looking for the next really big ideas?
Greg: Well, there's no doubt that drugs that activate the immune system are the bright, shiny yellow object. There's no doubt about that. And for good reason - cutting burning and radiating through surgery, chemo and radiation can not be the future of cancer - should not be. I have leukaemia. I had chemotherapy. With my particular leukaemia (CLL) nobody gets chemotherapy now and I was treated only four years ago. So now they all get a pill, no more chemo, which is great because it's a chronic condition, I'll probably get it again and I'll take a pill instead of chemo three days a month. So that's progress. But the other thing is when you activate the immune system, it is a beast. And what you don't know is, is it your beast or is it not your beast? And if we activate the immune system, it's hard to shut it down.
Greg: So you could get diabetes, you could get MS. You can get all kinds of autoimmune diseases and cancer, right? So we have to be, you have to be careful. Most people would trade diabetes for cancer, but they don't want to add it to cancer. So I think we will be dealing with the immune system now for a long, long time. And what I'm most excited about are antibodies that attack cancer cells that know if they're in a cancer cell or a healthy cell. And the reason that's important is that your healthy cells contain a lot of the same mutations as your cancer cell. So if your antibodies come in like just a shootout and they kill everybody, there's a lot of ancillary damage to healthy cells. But if they come in and they go, you know what, I'm not in a cancer cell, I'm not turning on and they can tell this through pH or the environment, or "Uh Oh, I'm in a cancer cell, all hands on deck, we're blowing this thing up". Then you don't get as sick from the treatment. So to me, the idea that a cell can look around and know where it is, is mind boggling, but people are doing that already.
Kat: That excites me so much because I've been researching a book about cancer and the more you look into it, the more you realize that our bodies are just patchworks of mutation. As we get older, everything kind of gets a bit dodgy. So the big question is like, what is cancer? And when is cancer? So actually deciding which is a bad cell and which is just a sad cell, I think is a really big challenge.
Greg: It's a huge challenge. We way over-treat a lot of cancer. And the reason is nobody wants to risk that their cancer is a watchful waiting situation instead of a full attack. But here's the problem. When you attack cancer, it often makes it worse. It's related to the war on terror. So when you drone bomb a terrorist group, the survivors become more radical, not less radical.
Kat: Yeah. What doesn't kill it makes it stronger.
Greg: Exactly. That's totally true of cancer. In fact, you have a system in your cells that knows when it's under attack, even the healthy cells, and what is their response? Their response is to take the cell back in evolution to a more vehement, awful state, sort of like what they call the reptile brain - road rage. So when a cell is attacked for cancer and the neighbouring cells are healthy, the neighbouring cell becomes the equivalent of a road rage cell and literally causes more stress and inflammation. So full on attack is not always the right thing.
Kat: Because cells just want to live. It's like cells just want to live - and that includes cancer cells.
Greg: And if they were girls, they just want to have fun.
Kat: That's really inappropriate.
Greg: A little Cyndi Lauper comment.
Kat: Finally, you've been part of the, the Moonshot for Cancer. We talk about magic bullets, we talk about miracle cures... What does the future cure for cancer look like? Because I sometimes think we've been a bit misled by some of this very bombastic language.
Greg: Yes. We were very careful in the Cancer Moonshot to make our mission very clear, which is to double the rate of progress against cancer and everything from how to prevent it to how to survive it. It was never that we're promising to cure cancer. And there'll be some cancers that we never cure, but you live with. Like my leukaemia - It's not cured, but it's in remission and it's been five years. So if I get it again, as I said, I'll take a pill. The challenge is every cancer is different. So there are some cancers that if you catch it soon, no big deal. Other cancers, liver brain, pancreatic, lung are hard to detect. And once you can see it, it's too late. So we have to get better at looking in the blood and figuring out from the detritus in the blood when cancer cells are starting to make a difference in your biology.
Greg: We have cancer cells all the time and they're sloughed off and they're eaten up. But when the cancer cells escape that first roundup, that's when you start seeing things in the blood. And that's why we started something called the blood profile Atlas consortium, which is what can you learn about the future of cancer in a given person based on what their blood looks like today. And when we get that done, then we'll be able to say your cancer burden is low, normal or high meaning something's going on. We're a long way from that, but that's where we have to go.
Kat: Greg Simon, former president of the Biden Cancer Initiative.
Progress in childhood cancer
Kat: Most of the focus on cancer research is aimed at adults. But given that September is Childhood Cancer Awareness Month, it’s also important to think of the children.
While cancers in children are mercifully rare, around 1,400 kids are diagnosed with cancer every year in the UK. And although survival is arguably now very good, with more than 8 in ten of them surviving for at least five years on average, it’s not good enough. And, of course, that’s in a wealthy country with all the advantages of modern medicine.
To find out where we’ve come in treating children with cancer, and where we need to get to in the future, I spoke with another special guest at the Manova Health Summit: Jim Downing - president and CEO of St Jude Children’s Research Hospital, one of the leading US centres for research and treatment of childhood cancers.
Jim: It's really quite amazing how far we've come. I've been at St. Jude 33 years and St. Jude has been in existence 57 years. And if we think back to when St. Jude was first established, really the most common form of paediatric cancer, acute lymphoblastic leukaemia, was really uniformly fatal, you know, less than 4% of kids would survive. And now if we come forward to today, a child entering the hospital in the developed world with acute lymphoblastic leukaemia has a 94+ percent chance for survival. And so that's in a single generation to take the most common form of paediatric cancer and convert it from incurable to curable. That's an amazing level of progress. And it was done before precision medicine, it was done with drugs that are old. Most of them were there when paediatric cancer was uniformly lethal. It was learning how to use those drugs, learning how to carry kids through the toxicities of those drugs and keeping them from dying of bleeding or from infections. So we've made great progress, but 80% cure in the developed world does mean one in five kids with cancer that enter the hospital are going to die of their disease. And so that's statistics. That's pretty shocking. And it still means that death from cancer is the major cause of death from disease in children between one and 15 years of age in developed countries.
Kat: So what do we know about children's cancer and how they're different from adult cancers? What have we discovered now?
Jim: You know from a historical perspective, we always knew paediatric cancers were different. There were types of cancer that occur in the children that we never see in adults and types of adult cancers that we never see in the children - lung cancer, prostate cancer, breast cancer, never occur in the kids, colon cancer, exceedingly rare in the paediatric population. Rhabdomyosarcoma, Ewing sarcoma, you know, certain kinds of leukaemias, certain kinds of osteosarcomas, paediatric brain tumours never seen in the adult population. So we know fundamental differences. We know most of the paediatric cancers really are not caused by environmental or lifestyle issues. They're really often mistakes of development that generate these cancers. But as we've progressed, and as we got into the genomics of paediatric cancer we at St. Jude 10 years ago started the paediatric cancer genome project. That was an incredibly ambitious effort to map the genome of 600 paediatric cancers and their normal tissue and to do this at whole genome sequencing. It was undertaking at a time when only one whole cancer genome had been sequenced. We thought we could sequence that many paediatric cancers over a three year period for a cost of somewhere around $70 million or $60 million, and that by doing that, we could gain great insights into the landscape of mutations that underlie paediatric cancer. So a major undertaking - the output of that was incredible. So in every single paediatric cancer that we sequence, we gain new insights and we gained really insights that provided answers to all of those questions that we posed: new subtypes of leukaemia were discovered, new genetic mutations and some of the incurable cancers. And then as we expanded that and did 700, and then we did, you know, 3000 paediatric cancer survivors. So now, if we look at all of those mutations that we see in paediatric cancer, how do they differ from what we see in adult cancer? And it turns out almost 50% of the mutations seen that drive paediatric cancer are never seen in adult cancer. And so that was really a shock that really said that these are being caused by fundamentally different mechanisms, that they were unique tumour types that were driven by unique genetic mutations. and that if we ever wanted to use this information to advance treatment, we were going to have to have focused efforts to develop treatments against those mutations and the pathways that they alter.
Kat: That's a really important point because from what I know about developing cancer drugs and testing them, it tends to be that you go for the adult patients first because it's a massive market. And then you kind of cast around and see, okay, are there any paediatric cancers that this works for - a sort of trickle down? So this tells you that that's not going to work?
Jim: Yeah, no, absolutely. It's not going to work. And so there are some tumor types that are in common, and so the trickle down has led to advances, and actually the reverse. If we think about the ALK mutations in lung cancer, well, the ALK mutation was first identified at St. Jude children's research hospital as a fusion in anaplastic large cell lymphoma in paediatric patients, probably 15+ years before the mutation was found in lung cancer. At that time we approached drug companies said, okay, here's a known kinase and known driver of this tumour type. We know that it's a sort of credentialed target that if you inhibit this kinase activity, you can inhibit the growth. No company was interested because the number of patients that would be available to use that drug was too small. And so it wasn't until it came into lung cancer that then they were able to use it. And by then ALK mutations were also identified in neuroblastoma and other paediatric populations and so that trickle back or trickle down did help, but it started in the other direction. So when we think of that landscape of paediatric cancer, how are we going to develop therapies against that? And drug companies will play some role, but it is going to take academic efforts to really understand the biology of those mutations and try to develop lead efforts to understand how inhibiting or bypassing those pathways might lead to vulnerabilities that can then lead to treatment against those cancers.
Kat: One thing that I do think is really interesting is the more we understand about adult cancers and the kind of spectrum of mutations that drive different cancers and realizing that actually many people's cancers are almost unique. And this idea that one size fits all, you can just treat thousands and thousands of patients with the same drug - that doesn't work. And you start to think actually many adult cancers are getting as rare and niche as many of the paediatric cancers. So this suggests that actually we need a whole rethink of how do we find new cancer drugs.
Jim: Yeah. And I think, you know, part of the lesson from that though, is that no single drug is really going to work. You know, there are the rare exceptions of cancers that respond remarkably to single agents, like BCR ABL positive, CML, et cetera, but that we're really gonna need combinations. It really is a variety of pathways that are turned on, those pathways turned down or turned off lead to other vulnerabilities. And it is this heterogeneity within the tumours that there is a variability within a single patient's tumour on what mutations are present, where within that tumour - over space and over time,
Kat: It sounds like an amazing picture of progress and an exciting future. But we mustn't forget that that is mostly focused on developed nations. The picture in the developing world is still very, very different. What's going on there?
Jim: Yeah. In the developed world there are several things that if one says, all right, how many kids are there in the world that get cancer? And so there are different groups that try to generate those estimates and it turns out the groups don't even agree on what the true denominator is for the number of children that develop cancer. As one sort of takes those data and does better simulations, the number keeps going up. And so it's estimated that 400,000 children across the world develop cancer each year, less than the majority of those are even diagnosed, most just develop cancer and die. In the United States about 16,000 kids with cancer. So we're talking a massive number across the world. And as healthcare systems, economies, political structures of countries improve children are no longer dying in early infancy from infections or from other diseases and so the number of children who might develop cancer increases and that number of cancers is going to increase even further.
Jim: So now we have a world where pediatric cancer is going to be increasing because kids are going to be living to that one to 15 year of age and not dying in that first year. We have healthcare systems that don't even know how to treat these children and aren't ready to treat these children. And if one looks at the economic impact in a country, you know, for life adjusted years, you're talking about a major economic impact because if you can cure them and we know we can cure 80% of them, that's the rest of their life that they can contribute to that economy. So, you know, how does one address that? How does one raise those cure rates, raise the infrastructure needed to treat children with cancer. And you can go country by country or region by region, but wouldn't it be better to pull everyone together and to really develop a global alliance where we can learn across the world at the same time, what works, what doesn't work, what did we learn from this culture that we might be able to transfer into this part? What are those experiments of nature that will give us new insights into cancer? Can we look at particular genetic subtypes of cancer in low and middle income countries where they won't be able to be treated as aggressively as they are in developed countries? And do they actually do as well? And are we over-treating in developed countries? So I like to say, if we organize this and we developed this global alliance, we will learn more from low and middle income countries than they will learn from us. Bringing everyone together, we can accelerate progress so that one day no child does die in the dawn of life from cancer.
Kat: An optimistic vision for the future from Jim Downing, from St Jude Children’s Research Hospital. And you can find out more about the St Jude Global Alliance for children’s cancer by going to stjude.org/global, or follow the links on the page for this podcast at GeneticsUnzipped.com.
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Analyse This
Kat: As Greg and Jim have explained, cancer treatment increasingly relies on insights from molecular testing. So - what does this actually look like on the ground?
Dr Marianne Grantham is the Head of Cytogenetics and Molecular Haematology department at the Royal London Hospital, at Barts Health NHS Trust.
She and her colleagues are tasked with testing many thousands of samples every year from patients in London and the Southeast of England with blood cancers - or haematological malignancies, to give them their scientific name - as well as solid tumours like bowel, breast or lung cancers, and all the rest. This could be to confirm a new diagnosis, to help doctors select the best treatment, or to see how their disease is responding to therapy.
I started by asking her how the technologies available to her (slightly noisy!) lab have changed over recent years.
Marianne: So we've seen huge changes in recent years in terms of the different techniques that we've been able to use, the actual genetic changes themselves, and our understanding of what we now need to look for, and also the number of cancers where genomics has become increasingly important. So what we're really seeing is a huge number of tests being performed, and it's going up year on year, we're seeing an increase. And like I say, the actual cancers that we can now test is increasing. So if we go back perhaps five years ago, we might have been looking at the odd PCR to look at a specific mutation, whereas in the more recent years, we're now using methodology such as next generation sequencing. So we're not just looking at one particular gene or one particular variation, but we're able to look at many, many different genes at once because now we understand how much more important this information is in the way we manage our patients.
Kat: And I guess the big question really is, does it work? Are you actually seeing changes and improvements in patient care, perhaps even in survival based on bringing in these kinds of new technologies?
Marianne: Absolutely. I mean, it's absolutely fantastic that we now have the opportunity to give patients different options based on the genomics. So rather than just using generic treatments, given to any particular cancer, we're actually able to really target that individual's cancer based on this genomic information and make sure that we're giving them treatments that are really going to work whilst avoiding unnecessary side effects. So for example, the treatment landscape for things like non small cell lung cancer has vastly changed as targeted therapies have become available. And also in hematological malignancies, we now know that biomarker specific therapies can really enhance patient outcomes and reduce those awful side effects that we know come alongside those aggressive and standard chemotherapies. So we're really seeing fantastic improvements in patient survival because we're really targeting the cause of that patient's cancer.
Kat: And what about the time it takes from when you get the sample to actually getting something that a doctor could say, okay, here's something I can base a decision on. I was talking the other day to Mike Stratton, who's the director of the Sanger Institute, and we were reminiscing about how long sequencing anything used to take, you know, a decade ago, two decades ago. How long does it take to actually get a timely answer that a doctor can then use to direct someone's treatment?
Marianne: Well you're. quite right, absolutely back in the day things used to take a really long time, we would be turning around results in a month or so, partly because the results that we were looking for at that time didn't have the same impact on patient management that they do today. And obviously as you can well imagine everybody wants things as quickly as possible. and certainly for patients themselves, the period of sitting and waiting to determine what's going to happen can be hugely distressing. So the sooner we can give people, our clinicians and our patients an answer and a definitive treatment plan the better. And so really we're trying to make sure that we can deliver our results as quickly as possible, and I would say that five to seven days is definitely achievable and in fact, nowadays you can even get that much faster within anywhere between 24 and 72 hours from receipt of sample to a meaningful result. And that really, really helps that clinician decide, what am I going to do with that patient and what options can I give them?
Kat: It certainly has been a difference from, I remember the early days of the studies talking about this when it was months to get a whole genome sequence from a tumour. And it's just incredible the advances in the technology that bring it down to a matter of days.
Marianne: Yeah absolutely. And as the technology improves and new systems become available, these results are going to be made quicker and quicker. So it's not unrealistic to think that we can have a meaningful genomic diagnosis within 24 hours, or even perhaps shorter in the future from receipt of that sample into the laboratory.
Kat: I've just finished writing a book that's all about cancer and evolution and genetics and how tumours are sort of genetically evolving systems. And one of the things that really became clear to me is that, although the idea of precision oncology and molecularly testing someone's tumour and using that information to shape their treatment is really exciting tumours change, they evolve resistance, and that it's not just going to be "we tested you once, that's a one and done" that there's going to be a need for retesting. So I guess if it's easier, if it's quicker and it's cheaper to do this, that also starts to become really feasible.
Marianne: Absolutely. And the great thing, for example about next generation sequencing technology is you're not limited to the number of targets you can test and the panels that you run can become flexible and can be adapted over time as we understand more about the different targets that we need to look for. And so we are already testing patients, not only at the beginning of the presentation, but perhaps after they've had treatment to make sure that their disease has gone away. And also, like you say, to look for those resistance mutations as clones change and evolve so that we can adapt our treatment to tackle that and new clone and that new disease. And we see that and are doing that a lot already in terms of solid tumours and non small cell lung cancer, but also in our haematological malignancies, we know that certain cancers develop these resistance mutations and we need to look for them to make sure that we tailor our treatment accordingly,
Kat: All this genetic testing technology - it does sound really complicated. I think I've got in my mind the idea of some enormous beige box with lights and bleeping things on the front. How complicated is this technology? How accessible would it be to a hospital that's not as big and flashy as the one that you work in?
Marianne: Absolutely. I completely understand, and I felt exactly the same way several years ago. It feels that it might be intimidating, but actually the advances that have been made with this technology is that really isn't the case anymore. The developments that have been made are amazing, and the people that have thought these machines up and this technology up - it's just phenomenal, the way that they've been designed to be so streamlined and efficient, that they really are very much a plug and play kind of approach and the associated software and computer programs that you can access to accompany your machinery means that you don't really need to be that super bioinformatics boffin that perhaps you used to need, and that these technologies really are accessible to a pathology laboratory that don't have their own specific genomics department. And that's really, really fantastic in terms of enabling the equity of access to patients no matter where they are.
Kat: And finally looking for your sort of vision to the future, what would you like to see the patient care pathway looking like incorporating all these genomic technologies? What is the cancer care vision of the future as far as you're concerned?
Marianne: It's definitely a very exciting time and a real vast improvement on years gone by. And I think having really comprehensive genomic profiling available for our patients, it's so critical, but having that in that timely fashion, so not having to wait now months and months, or even weeks and weeks for that data, but having it in a real clinically appropriate time and understanding what to do with that information. Something that is very important is understanding that genomic data in isolation is often meaningless. And it's really important that we integrate that information with other disciplines within pathology and within the patient pathway. So using it in conjunction with our morphology, our histology, our immunophenotyping, so we can integrate it together to give the patient the most effective diagnosis and treatment plan going forward and really mainstreaming that genetic data. I think it's going to be critical for the future. I think genomics has got a really exciting and important place in a modern healthcare service.
Kat: Marianne Grantham, from the Royal London Hospital.
On To The Next Generation
Kat: As Marianne says, time is of the essence when it comes to the journey from a patient’s cancer sample to an actionable report on their doctor’s desk. We’ve certainly come a long way from the days when it would take months to genetically analyse a tumour sample, but when it comes to treating cancer, every day counts.
Kim Wood is from Thermo Fisher Scientific’s Clinical Sequencing Division, working on next generation sequencing and the technologies that can be used by pathology labs to analyse tumour samples and help doctors decide on the best course of action.
Right now their latest sequencing machine, Ion Torrent Genexus, is still being put through its paces in research settings - meaning that it’s currently designated for research use only - but plans are under way to get it approved for routine medical use in Europe and the UK within the next few years.
So, what does the future look like for the use of genetic and genomic technologies in cancer? I asked Kim to gaze into her crystal ball… or rather, her Genexus machine.
Kim: It's actually something that we're really, really proud of. It's the world's first turnkey next generation sequencing system. So if we put it into context previous next generation sequencing systems that have been on the market in the past, in order to get to that end result there's actually modular pieces of equipment that are needed in order to get that result. So there's lots of user interaction - preparing that sample for analysis, the sequencing, etc. What Genexus is is a fully integrated system. So it's one unit that does everything.
Kat: So what advantages does this new system have for users? What, is the future of this process actually going to look like in a lab?
Kim: So some of the things that this new system can do is it's a really, really quick touch point at the beginning. So you walk up to the system, you place your extracted nucleic acid onto the system, along with reagents that are cartridge based. And that takes no more than five minutes and believe me, we've timed it. You close the door, you start the running, you walk away and it's as simple as that and the results become available within 24 hours and they're meaningful results.
Kat: So the important thing with any of these kind of tests is that the information that comes out is actually useful, that doctors can take it, look at it and think, okay, I can construct a treatment plan for my patients. So with these new technologies that are coming online and coming soon, what kind of outputs will come from that? What sort of information can doctors expect to be able to get?
Kim: We've worked really, really hard to make all of our systems a solution based system and for it to be as user friendly as possible. So that includes not only providing the technology for assays as well as what this system generates is not just a bunch of raw data. That's meaningless. It actually, we provide the tools that are needed to make sense of that data and to slim down that data into something that's meaningful.
Kat: And how long does it take to get that kind of data?
Kim: So, this is the huge step change for us, and it's something we're incredibly proud of. So if you are in context of a previous systems that have been on the market, that the quickest time period that we've seen for next generation sequencing systems has been four days, but routinely up to two weeks. The Genexus integrated sequencer provides a sample to report within 24 hours.
Kat: This may be a bit of a 'how long is a piece of string' question, but when do you envisage that this technology might actually be available for clinical use? Because it sounds amazing if you can cut the time to getting an answer, getting something meaningful, to help guide patients' treatments. So how long are we looking at?
Kim: For Genexus you are completely right, it's how long does a piece of string. We're we're actively going through that process now, the process is quite lengthy - as it should be to register for a medical device - but we do have a timeline in place. And so we're committed to register the Genexus system in Europe quite soon.
Kat: So fingers crossed.
Kim: Yeah, definitely. We're really excited about it.
Kat: And just broadening out a bit, what are your hopes for the future of this kind of technology? What would you like to see for the future of cancer diagnostics and cancer treatment personally?
Kim: I feel incredibly lucky to work where I work and I suppose that can come across. I'm blushing as I'm saying it, but it's a personal journey for me, and it's the personal journey for many of my colleagues that work within this division of ThermoFisher. I've recently witnessed my mom being diagnosed with cancer. She had treatment and then she relapsed. And everybody's experience with cancer is different, but for my family, the most agonizing time was waiting for the results. And during this time we just realized just how impactful this paradigm shift of precision medicine and precision oncology has to change the outcomes of cancer patients in the future. And I can honestly say that during that time of realizing that she'd relapsed with cancer before we could get to "these are the test results, this is the plan, this is the way we're going to move forward with the treatment, and this is the backup plan" - that for me, was the most agonizing period that we've been through, actually more so than the treatment itself. And so for me, anything that can provide or facilitate a step change in precision oncology and also speed up that result and accessibility to the most comprehensive genomic profiling to give the most actionable results in a short time period, from a personal opinion, that's for me is the most exciting thing.
Kim: So being able to work with a team that's passionate about this, and it's not just a vision that we've sat around the boardroom and said, yeah, this is what we're going to go for. It's made up of, uh, people that work within this team that have had personal experience, both in cancer and in other diseases where precision medicine in general can provide step change.
Kat: Kim Wood from Thermo Fisher Scientific. You can find out more about their new Genexus system, which is currently for research use only, at oncomine.com/genexus-oncology and there are more links to information about the transformative power of genomic sequencing for the future of cancer treatment on the page for this podcast at GeneticsUnzipped.com
Find out more:
Meet the monkey flower
Kat: And finally, it’s time for a quick look at what’s in the latest episode of the podcast from Heredity, the journal of The Genetics Society.
For more than a century geneticists have relied on model organisms - specific species of animals, plants and microbes that have been characterised and studied in great detail. And if you’re a plant geneticist, you’ve probably heard of arabidopsis thaliana - which we talked about back in episode 7 of our very first series. But now there’s a new model plant in town - the yellow monkeyflower, or Mimulus guttatus to give it its full name.
In this episode of the Heredity podcast, host James Burgon chats with Alex Twyford from the University of Edinburgh about the complicated genetics of these curious plants, and explores the issue of ‘plant blindness’: the unfortunate tendency of biologists to overlook the research value, and potential, of plants.
James: If you're out and about doing field work in the UK or walking on the Riverside, you might see monkey flowers, they've become widely naturalized in the UK, but they're native to North America. And they're really exciting because they're emerging as a novel model system for studying evolutionary and ecological processes. So we have Arabidopsis as one of our main plant model systems, but you can't do everything with one plant and monkey flowers are really fascinating because they occur all the way from the Mexican border up to the North in Alaska. And across that range, they show amazing variation in their ecology. So you get some plants which are grow thermal hot Springs, where the soil is literally bubbling with boiling water and they've adapted to that environment. You get other populations which grow in copper mines, and they've adapted to copper in the soil. And then some populations which grow right on the sea front, and they're exposed to really salty conditions.
James: And I think it's that ecological variation which has captured people's attention over the last 50 years. If I'm lecturing students, they may come up to me afterwards and say, "Oh, I enjoyed your lecture. I've always found plants boring because all people talk about is stomata or phloem and xylem." And I find it disappointing because so often we're focusing on those mechanistic differences - which are interesting, I'm not downplaying that - but they're not the things that really excite me. And for me as a plant biologist, and I'm proud to call myself a botanist, there's a lot of really exciting aspects, and most of them around plant diversity. So there are hundreds of thousands of different plant species, and the ecological variation is remarkable. All you have to do is walk in any natural environment, particularly somewhere like a tropical forest, and you'll be surrounded by hundreds of different plant species, all adapted to different conditions and interacting in different ways. So I think that what we call plant blindness, or lack of plant awareness, is disappointing. And I suppose I'm trying to inspire other people to open their eyes and to think more about plants because there's a lot we can learn from plants that we can't learn from vertebrates.
Kat: You can find the full interview in the latest Heredity podcast - just search for Heredity in your favourite podcast app.
That’s all for now. Thanks very much to ThermoFisher Scientific for sponsoring this episode of Genetics Unzipped - and if you’re interested in sponsorship opportunities, just drop me a line at podcast@geneticsunzipped.com
Guests:
Greg Simon, past president of the Biden Cancer Initiative and former executive director of the White House Cancer Moonshot Task Force.
Jim Downing - president and CEO of St Jude Children’s Research Hospital
Dr Marianne Grantham, Head of Cytogenetics and Molecular Haematology department at the Royal London Hospital
Kim Wood, Thermo Fisher Scientific’s Clinical Sequencing Division
Image credit:
DNA sequence of CCR5 Delta 32 gene mutation. Emei Ma, P/C Guy McLoughlin. Attribution 4.0 International (CC BY 4.0)
We’ll be back next time with more from the world of genes, genomes and DNA - and before that, there’s another bonus episode of Genetics Shambles to fill your ears.
For more information about this podcast including show notes, transcripts, links, references and everything else head over to geneticsunzipped.com You can find us on Twitter @geneticsunzip and please do take a moment to rate and review us on Apple podcasts - it really makes a difference and helps more people discover the show.
Genetics Unzipped is written and presented by me, Kat Arney. It is produced by First Create the Media for The Genetics Society - one of the oldest learned societies in the world dedicated to supporting and promoting the research, teaching and application of genetics. You can find out more and apply to join at genetics.org.uk Our theme music was composed by Dan Pollard, and the logo was designed by James Mayall, and audio production was by Hannah Varrall. Thanks for listening, and until next time, goodbye.
