With the ever-increasing potential of new technology and the exponential growth of the life sciences field, researchers are always running into new problems to solve. In this interview series, we get scientists’ opinions on the ‘Big Challenge’ in their field and the steps being taken to address it. From new and unique hurdles to fresh takes on common problems, we dive into the complexities of the research landscape.
In this interview, we chat to Simon Heeke (Assistant Professor, Thoracic Head & Neck Medical Oncology, MD Anderson Cancer Center) about the big challenges in the liquid biopsy field, particularly clinical implementation.
FLG: Could you introduce yourself and tell us a bit about your background, your role, and what you’re currently working on?
Simon Heeke: My name is Simon Heeke. I’m an Assistant Professor at the MD Anderson Cancer Centre. I work in the department of thoracic head and neck medical oncology, working on lung cancer and head and neck cancers. Among other things, I’m leading our translational liquid biopsy working group. Liquid biopsy is a big, big part of my work, from developing technologies that we can use to address certain biological and clinical questions, to how we can implement them and use them within our clinical trials. So, really, [I work on] everything from the tech development to the application side.
Outside of liquid biopsies, I’m also working on identifying transcriptional biomarkers. We know that there are targeted, genomic alterations, like EGFR mutations or gene fusions and we’ve been quite good at developing genome-level therapies for these. Undoubtedly, this is something very important within the precision medicine workflow. However, there’s also an increasingly large body of cancer states that are not defined by genomic alterations, but by what I would call transcriptional states, meaning the biology of the disease is phenotypically different. For example, in small cell lung cancer subtypes, we discovered that there are four transcriptionally defined states that we defined and developed biomarkers to identify, which we are now able to bring into a clinical setting through a CLIA validated test.
But this is more, for me, of a poster child. Of course, this is a great achievement and clinically very relevant. But the more I was working on it, the more I realised that those subtypes – which are less defined by genomics and more by complex states – seem to be occurring in many other cancer types as well. So, now I’m really working on expanding these across other cancer types, with a focus on rare cancer types. We see there’s a big scarcity; they’re not really studied because we don’t have the biomarkers, leading to a ‘chicken and egg problem’. However, we are demonstrating that we can develop biomarkers, not just from tissue biopsies, but also from liquid biopsies, providing the opportunity to bring them into the clinical setting. So far, I’ve seen a lot of excitement around this, and hopefully we can use this to advance a new generation of biomarkers for precision medicine.
FLG: I can see why you’re so busy! Liquid biopsy is obviously a really exciting field. There’s a lot of anticipation, as you have demonstrated. What would you say is the biggest challenge that you’re experiencing with liquid biopsy currently?
Simon Heeke: I think I can break it down very easily into clinical implementation. Of course, liquid biopsy plays a very pivotal role in many clinical settings. Speaking of lung cancer, nobody will doubt, for example, the utility of liquid biopsy for the detection of resistance mechanisms to EGFR. We all know about T790M, we all know that we can use liquid biopsy to the detect them. But when I think of liquid biopsy as a whole, and the more I work in it, the more I see a disconnect between researching very fancy, novel technologies and seeing those technologies actually getting implemented into the clinic.
To give some examples, we know that we can detect genomic mutations and we can detect them in a lot of different cancer fields. But still, we know it’s not happening everywhere. This is, for me, some of the most basic implementations of liquid biopsies. We know that liquid biopsies are increasingly used at progression or when you have patients treated with, for example, targeted therapies. But even when I speak with my colleagues, some are still doubtful about how we can use it. Think about MRD, for example. Now, we have a guide document from the FDA about how we can introduce liquid biopsy, and there are dozens, if not hundreds, of clinical trials that demonstrated that MRD is a good surrogate for the prediction of relapse. But how often do we see a clinical treatment change based on these methodologies? How much do we see them actually being used in routine clinical care? We have fantastic technologies that have seen approval from targeted therapies to therapeutic resistance. Last year, we had the first approval of a liquid biopsy test for cancer screening for colorectal cancer. But I still believe that despite those technologies and the headlines that we see everywhere, the real clinical implementation of liquid biopsy for every cancer patient is increasingly lagging behind. And I think we have to do much, much more work to really translate our findings and get approval for a technology to turn it into something that affects the clinical course for patients treated for cancer. For me, the biggest challenge right now.
FLG: I’m hearing this echoed by other people; it definitely seems to be a major challenge. What can we do about it? And what if money wasn’t a barrier?
Simon Heeke: I think we have to tackle this on all ends. There’s still a lack of education, which is one of the less expensive problems to solve. But I want to be honest on both ends; there’s a lack of education when it comes to showing the opportunities of liquid biopsies, but I’ve also seen the other side of it, where I feel like certain technologies were overhyped so much that they actually created, in the end, something of a disappointment for the people using it, when they realised that the technology wasn’t able to give everything that it promised. So, I feel like first, education from both sides – ensuring that people understand the promises, and what we can do right now with liquid biopsies – is very important. But also, being very mindful on the other end, of not going into an overhyped struggle where we say liquid biopsy can do everything, and it will change the world. I think we need to maintain laser focus on educating people about what liquid biopsies can achieve now, at this moment, without neglecting what liquid biopsies can achieve in the future. Being mindful that what we do in a research setting or in a clinical trial at a major cancer centre can be very different to what a treating oncologist can achieve in another setting.
I also feel it is important that we tailor our research towards questions that lead to clinical change. For example, I think it is very important that we continue to focus our energy on developing liquid biopsies as a predictive biomarker. We have done a lot of research where we show what we can do, but we have to do much more work on really using liquid biopsies as a predictive biomarker. How can we use it to make a clinical decision? I’m not saying that those other questions, like surveillance or classification, are not important. Don’t get me wrong there. But I think if we want to move forward, then I think now’s the time where we have to consider the clinical question and identify the right technology to answer it. Not doing the inverse; developing a technology and then chasing what clinical questions we can answer with it. I think it’s important that we really try to find a clinical question and then give our best to address it from a biomarker standpoint. That can be achieved using liquid biopsies, and I think there’s a high probability that it will be liquid biopsies. But I think we also need to be open for other potential solutions. And what I’ve learned with our predictive biomarker work is that we were successful in small cell lung cancer because we really needed biomarkers there. We were able to develop these biomarkers and were able to bring them into a clinical trial. Now, I speak with other clinicians – I have people emailing me about cancer types that I have never heard of before saying, ‘This is great, what you did there. We need this.’ Historically, there’s been a lack of research in these areas because there was never the technology to do it. But now that we have the technology – and despite the fact that wasn’t developed for necessarily addressing that question, we can tailor it to match. Not to say that all the other research is not important. But I think we as a field, we have to remain focused on developing technologies to address biological or clinical questions.
FLG: Each disease is going to be different and have its nuances; going after the biology seems the most logical way to do it. Do you have any advice for someone who’s trying to break into liquid biopsy field?
Simon Heeke: I was actually the young committee chair at the International Society of Liquid Biopsy for some time. A big part of my work was trying to bring young people into the field and get them excited about liquid biopsies.
The general advice, I would say, is when you do biomarker research or work on precision medicine, then the chances that you come cross liquid biopsies are very high. So, don’t be shy. Don’t be afraid that this is a closed field where you have to be an expert in everything before you break into it. It is one of many methodologies that we use within precision medicine, and irrespective of whether you’re in drug development, or biomarker development, liquid biopsy will likely be relevant. When you’re a young physician, probably working on your first clinical trials, you may be wondering what you can do. Or if you’re nervous as it’s the first or second clinical trial that you’re working on, don’t be shy about including liquid biopsies. Reach out to folks that you’ve seen who are working in the field. Reach out to all the societies, which are there when you need advice. Shoot me an email; I’m happy to chat about this. But don’t be shy about working on it. When you don’t know the technology, you can still bank plasma and then think about this later. Be brave, start somewhere. You don’t start with the most perfect solution.
When you are doing a PhD, probably working more on the translational, maybe tech development side, it’s the same thing. Many of the methodologies that we’re using are the same. If you have done some sort of sequencing for your tissue samples, the probability that we use the same technology in liquid biopsies are very high. You’ll need to learn some specifics, such as some of the limitations that we experience, but it’s not a hard transition. If you have an idea, just try it out.
But I think what’s important for me in 2025, after we’ve done so many decades of liquid biopsy research, is not to think about liquid biopsy as a replacement for something. Think about liquid biopsy as something that adds something new, rather than answering the same question differently. Think of liquid biopsy as a way to give you an answer to a question that you couldn’t answer before. Use it as something new. We can be creative; for example, we have liquid biopsy from saliva, which a patient can collect at home. Or you can have a mobile phlebotomist go to your patient at home and take the sample there. I think there are many opportunities when you think about liquid biopsy as a new, cool way of doing things. But don’t be afraid that it’s something super complicated. And just to add there, I know most of the stuff is tailored around oncology, and I’m working in oncology myself, but liquid biopsy is not specifically for oncology. Probably the largest use of liquid biopsies is with NIPTs and pregnancy. But we also see liquid biopsies in the organ transplant setting and in many other disease types. So, don’t think this is the thing that people do only in oncology. If you work in neurological diseases, transplantation or other settings, this is also relevant for you.
I will now make a bold statement, that I think liquid biopsy will be useful in almost all disease settings. Therefore, whatever you do in precision medicine, not just precision oncology, be bold, try it out. There’s nothing to worry about. And it’s a nice field. It’s a very dynamic field. Novel advances are happening by the week, not by the year. I feel like this is the right time, if you want to get involved. There’s probably not one week where we don’t see novel technology or applications happening.
FLG: It’s great to see that liquid biopsies are being researched in other areas that would benefit from non-invasive testing. A final question – you are speaking at The Festival of Genomics and Biodata in Boston; what are you most excited about for this event?
Simon Heeke: It’s a very interesting event because it includes the academic side and the industrial side. We have biotech, pharma and academic researchers present; the exchange there is really what I look forward to, because we all need to be mindful to avoid working in siloed settings. Not ‘I work in this room and the other person works in the next room’, but we are all working to ultimately bring novel therapies and novel precision medicine approaches to the patient. I think that’s the overarching goal that we all have. And I strongly believe that we can only achieve this when we are all working together. So, I think this really strong interdisciplinary exchange that we have at The Festival is very important, not through just the presentations, but also through roundtables or discussions. Hopefully, by developing novel ideas, approaches and infrastructural frameworks together, we can be quicker and more tailored in our work. Where I think The Festival stands out, is that it’s mostly free to attend. Even if you might not be an expert in the field, it has such a low barrier to get involved, attend some sessions and leave with new ideas. I really hope it will also attract new people to the field because, as you can tell, I’m very excited about precision medicine. I want more people to feel the same. And I feel like this is one of the places where there’s a pretty high likelihood that after the event, you will feel the excitement too.
Want to hear more from Simon Heeke? Come and hear him speak at The Festival of Genomics and Biodata!
