Prof Tony Ng is an oncology pioneer, renowned for his molecular imaging work and expertise in medicine, immunology, cancer cell biology, biochemistry and statistics. Here he discusses his career and the importance of his recent transition from academia to industry for cancer research, as well as his current work as SVP and lead of GSK’s Oncology Translational Research organization.

The start of the 1990s was marked by the fast-growing HIV epidemic, with millions of infections spreading around the world and AIDS rising as a leading cause of death in young adults. It was in this escalating crisis that Professor Tony Ng first started his career as a practicing physician, after completing a medical degree at the University of Aberdeen in 1989.

Tackling a challenging disease for which there was not yet a cure, Professor Ng found his first speciality in immunology, infectious disease and oncology as he focused on the opportunistic infections and tumours that were prevalent among HIV/AIDS patient populations. But wanting to do more than just treat patients in the hospital setting, Professor Ng, with Professor Anthony Pinching as his clinical mentor, started a PhD in Immunology at London’s St. Bartholomew’s Hospital.

A drive to understand the complexity of patients

Professor Ng began this work with a growing interest in the interface between biology and disease from his clinical and translational work with HIV/AIDS – particularly in understanding the complexity of human patients and the immune system.

“Professor Pinching was an active clinician, so my training started with learning about the disease from patient samples,” says Professor Ng. “In those days, you were looking for a correlation between measurements in the lab and the clinical characteristics and/or progression of a patient. Let's say a patient has AIDS, what do their T cells do biochemically? How do their T cells behave differently compared to the earliest stage of infection? What might be the mechanisms that give rise to the immunological heterogeneity in these patients?”

But understanding the origin and significance of the broad variability observed in patient populations required more advanced methods than standard correlative analysis. “If you study quantum mechanics, the data are very clear cut. Measurements have small error bars. But if you look at different patient samples, whatever you measure generates much larger error bars. The question was, how do you truly understand that variability to find a solution or remedy for the disease? How do you account for it biologically? Professor Pinching and I had a shared interest in understanding that in more detail, as we both believe in the power of human biology.”

Tony’s clinical training also involved a clinical attachment in San Francisco, a city that suffered from a large number of HIV cases and had one of the greatest incidences of AIDS in the US in the early 1990s [ref]. “It brought what we were seeing in the lab into real life. There were a whole host of secondary infections and cancers such as Hodgkin’s lymphoma and Kaposi sarcoma where you could see differences in patients and their response to treatment – and it was clear that there was no magic bullet to cure all. This is where I really started to learn that it’s not just about the response of cancer cells, but also the response of the host as a whole.

This was a significant turning point in Professor Ng’s career as he focused his attention on new technologies to develop more advanced quantitative methods to better understand and characterize patient heterogeneity. But his experience was also foundational in highlighting the importance of integrating fundamental research within clinical care.

"San Francisco General was a fantastic hospital environment and the level of care for patients was excellent – they worked with no stigma or prejudice, despite whatever was happening in the external environment. The residents might have been up with patients all night long, but they were relentless in their efforts. There were no mobiles or iPads in those days, so everyone had a small pocket pouch where they kept written notes on the latest clinical trials and treatment recommendations for the opportunistic infections and/or cancers that we were seeing. No matter how tired the residents were, they made sure they had the latest information ready so that they could tell the attending physician the latest trial results and the best way to treat the patient.”

“I would also see academic roundtables/grand rounds, where clinicians would present case histories and scientists would talk about any relevant clinical trial results or emerging therapies,” Professor Ng continues. “That kind of clinical translational science cooperation was very inspiring. It was essential training early on in my career. If I had only done fundamental research as a physician–scientist using preclinical models, I wouldn’t have the same level of comprehension or appreciation of how to tackle disease in these broad clinical populations.”

Innovation in molecular imaging and oncology

As Professor Ng finished his PhD, signal transduction was emerging as a major scientific discipline, alongside systems biology. Understanding the signalling pathways of genes and proteins within cells, as well as signalling between cells, presented a level of complexity that could not be explained by simple correlations and linear interactions. It was the perfect problem for a more quantitative approach and motivated Professor Ng to continue his research in the field of oncology as a physician scientist, with particular interest in translational trial research.  

Professor Ng began with a postdoctoral position at the Imperial Cancer Research Fund (now Cancer Research UK), before joining King’s College London (KCL) as a Clinician Scientist. While at KCL, Professor Ng established himself as a pioneer of molecular imaging for the visualization and characterization of molecular (gene and/or protein) interaction networks. He made significant contributions to the development of imaging techniques for cancer diagnostics, particularly in the use of antibody-based fluorescence resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) to study protein interactions in cancer and immune cells.

Using this technology, Professor Ng and his mentor Professor Peter Parker, along with their close collaborator Professor Philippe Bastiaens, were the first to analyze signal transduction in cancer tissues. This approach not only deepened the understanding of the molecular mechanisms of cancer, but also paved the way for the development of targeted therapies that can precisely disrupt aberrant signalling pathways. More broadly, these techniques have established a rigorous platform for cell and tumour analysis, enhancing the precision of molecular imaging in cancer research.

Professor Ng was later appointed as Head of the School of Cancer & Pharmaceutical Sciences & Comprehensive Cancer Centre at KCL (2017–2023), and currently holds the position of Richard Dimbleby Professor of Cancer Research. He also served concomitantly as Professor of Molecular Oncology at the University College London (UCL) Cancer Institute and has led several other key projects and collaborations cross-institutionally.

This includes his role as director of the CRUK-funded KCL–UCL Comprehensive Cancer Imaging Centre (CCIC; 2008–2019), which integrates multidisciplinary teams to develop advanced imaging technologies and methodologies to improve diagnostic and therapeutic strategies for cancer patients. He also contributed as the KCL lead to the UCL–Barts–King’s–Crick CRUK Major Centre/City of London Centre, focusing on enhancing biotherapeutics​.

In recognition of his multidisciplinary contributions to cancer research, Professor Ng was elected as a Fellow of the Academy of Medical Sciences in 2013, and a Fellow of the European Academy of Cancer Sciences in 2017​.

Bridging from academia to industry to advance cancer research 

Despite Professor Ng’s achievements in academia and the public sector, he recognized the need for a shift in his approach as he sought deeper insights into patient heterogeneity and opportunities to apply his learnings in the clinical setting.

“As Head of the Comprehensive Cancer Centre at King’s College London, and due to my background in systems biology, I formulated a strategy to learn more about the mechanisms behind patient heterogeneity, focusing on understanding human biology,” says Professor Ng. “While you can study heterogeneity by observing cancer cells or patients in a steady state, you can learn a lot more if you introduce a perturbation such as a drug treatment and analyse how the system or network re-establishes a new equilibrium state. The only way to do that, and to collect data before and after treatment, is through a clinical trial.”

Professor Ng spent the next few years forging partnerships with pharmaceutical companies so that he could access various clinical trial and biomarker data. This involved writing proposals to support predictive biomarker research on stored samples from investigator (ISS) and sponsored trials. In 2021, these industry explorations took him to GSK.

“Tony Ng and I first met at London Tech Week,” recalls Tony Wood, Chief Scientific Officer at GSK. “We hit it off immediately and started exploring broader interests soon thereafter. I’ve always liked that he thinks about cancer in a very logical way and absolutely gets the importance of mechanism and biomarkers.” Professor Ng was subsequently introduced to others such as Kim Branson, SVP and Global Head of AI/ML; Anne-Marie Martin, SVP and Global Head of Precision Medicine; and Hesham Abdullah, SVP and Global Head of Oncology R&D. These early interactions paved the way for a five-year partnership between KCL and GSK [ref].

“When I first started discussions with GSK, what stood out to me was an instant chemistry and shared interests when it comes to clinical medicine,” says Professor Ng. “I was also very impressed by the thinking of the leadership team. Tony Wood was very visionary in the way he viewed research, and when I first met Kim Branson my first thought was that working with him was going to be fun. His neurons seem to fire a few hundred times faster than most other human beings, and I remember working hard to keep up with him. But we were very aligned in how we wanted to tackle cancer from a systems perspective and help transform patient care. We came from two different disciplines but our ideas seemed to collide and converge, and that made for a great way of working.”

The KCL–GSK partnership involves the use of machine learning (which covers a multitude of methodologies) to develop personalized cancer treatments by investigating the role of genetics and other patient and non-genetic biological factors. There is particular focus on patient stratification and increasing response rates to immunotherapies, for which progress is critical as currently only 20% of cancer patients respond well to monotherapy [ref].

“We entered the research collaboration with Tony’s KCL lab while I was leading my former Experimental Medicine team – our initial work together focused on testing a PARP inhibitor in organoid models of non-small cell lung cancer to generate multimodal data that could better inform biomarkers of response and resistance,” says Anne-Marie Martin. “Tony’s team were at the forefront of translational research, leveraging human-derived predictive models that were better representatives of the treatment and disease paradigm to inform biomarkers of response and resistance. Since joining GSK, Tony has evolved this work and is building the capability to enable a new way of drug discovery and development in oncology.”

Professor Ng joined GSK part-time in 2022 but has steadily increased his hours while retaining a professorship at KCL. “Although I love my career at KCL, there was never any doubt that I needed to work between industry and the clinical setting – this type of public–private partnership is essential to truly understand patient heterogeneity and improve patient outcomes. Hospitals do not make drugs, and pharmaceutical companies do not have hospitals. Once I realized this need, it was just a matter of choosing which company to join. With GSK, I could see the opportunity to bring what I had learnt throughout my academic career into the clinical setting, and that people like Tony, Kim, Anne-Marie and Hesham shared the same vision and appreciation for new methodologies and technologies.”

Kim Branson adds: “I often joke with Tony that his research life was going on nicely until I came along and ruined it. I remember predicting that he would have to join GSK while at our first dinner together. He did and I am very glad. He is a terrific colleague and friend.”

Thinking in reverse: translational research and digital biological twins at GSK

“What I remember about my first real day in industry is feeling quite lost. I was given a desk, an admin support and a broad remit to support the growing oncology organization,” Professor Ng recalls. “I decided that my first priority should be building a network in GSK. Through a little stroke of genius, Tony Wood and I created a Scientific Exchange Forum for oncology. It happened monthly at GSK’s AI/ML site in London, with some others joining online. It started as a very open forum – there was no set structure other than a general focus on the principle of reverse translation.”

Conventional translational research aims to convert results in basic research into results that directly benefit humans. It is a linear process that starts with discovery in the laboratory and ends in a clinical trial, but it has many pitfalls and a high probability of failure. In contrast, reverse translation starts with patient experiences in a clinical trial and works backward to uncover the mechanistic basis for any responses or observations. Research becomes a continuous cyclical process, in which each new patient observation stimulates new hypotheses that help refine and direct the next iteration of therapeutics research, which, in turn, leads to the next clinical trial. At GSK, the move towards reverse translation is part of a broader shift towards a more dynamic research approach that is taking place across its R&D organization.

“We designed the forum in such a way that we had GSK’s clinical development experts in the room so they could tell us directly about any challenges they faced. We also gathered representatives from many other disciplines – from research scientists to IP lawyers – so that it was truly multidisciplinary from the start. It was not restricted solely to senior people either, so we had the people who were on the ground doing the execution. The forum has now grown from a group of 20 to include more than 180 people, and it has really been integral in innovating our approach to clinical trials. It was also this that laid the foundation for GSK’s Oncology Translational Research group – it provided the network and connectivity to the rest of R&D that has enabled it to function so well.”

“Tony Ng has made fantastic progress in setting up his group to scale the work he started in academia,” adds Tony Wood. “I'm also tremendously excited about the potential collaboration opportunities with deep scientific experts such as Professor Sabine Tejpar, whose work in understanding colorectal cancer is world leading.”

Professor Ng is now Senior Vice President of GSK’s Oncology Translational Research organization that started in January 2024, and leads a key organization in Hesham Abdullah’s team. “Tony has been a great addition to the Oncology leadership team, and I know I speak for many across the organization by saying his expertise and leadership is inspirational. Together we are pushing the boundaries of science to address unmet need across haematologic malignancies, gynaecologic cancers and other solid tumours.” Dr Abdullah goes on to say: “Tony’s patient-centred mantra and his innovative collaborative approach, backed by the latest data and technology, will help us pinpoint genetic or immune signatures for various cancers and potentially find new treatment combinations to match the right medicine to the right patient. This will accelerate and optimize the next generation of cancer medicines for patients – now and in the future.”

Professor Ng is currently leading the Oncology Digital Biological Twin (DBT) project. This involves creating a biologically detailed reconstruction of a tumour or organ from patient samples to study disease progression and test different interventions. “It’s not good enough just to look at whether a drug will kill cancerous cells or tumours,” explains Professor Ng. “Because we know there are resistant cells in which the signalling network is completely rewired. This not only effects the tumour cell itself but also the tumour microenvironment, including the immune system. So we need to model and measure all of these different components to understand what the tumour is doing and how the patient is responding, and how effective the drug really is.”

Professor Ng and his team use the human-derived organoid or other surrogate material to collect thousands of multi-omics parameters for the cancerous cells and tumour microenvironment (and their changes under perturbation by drug treatment), employing various sequencing technologies and multimodal imaging approaches. The data are filtered and analysed using machine learning to focus on the most clinically relevant biological parameters (often from different omics spaces e.g. an admixture of RNAs and proteins), so that the team can understand the system as a whole. By translating findings from the organoid or surrogate to the patient, the goal is to predict what will happen in the clinic – including each individual’s response to treatment and the likelihood of remission or relapse, as well as understanding potentially targetable mechanisms in treatment-resistant patients (find out more about the DBT approach [ref]).

Professor Ng believes that the approach has the potential to increase the accuracy of patient stratification to improve the success rate of both tumour-targeted and immune-based therapies, or their combinations. Observations from early experiments indicate the feasibility of predicting patient outcomes (prognosis) from the multi-omics data, but the next step is to validate the approach in clinical trials and demonstrate an upwards trend in patient response rates following treatment.

“I would consider it a fulfilling career if we can make meaningful progress in understanding human heterogeneity, evidenced within GSK’s clinical trials. Reaching a stepwise increase in patient response rates will mean that we are on the right track and set the direction of travel not just for GSK, but for the industry,” says Professor Ng.

Removing barriers in academia and industry for better translational science

Professor Ng believes that working across both academia and industry has shown him where the current limitations are for translational oncology. “Our understanding of science has advanced so much in recent years, but many clinical trials seem to lag behind these developments. To achieve optimal outcomes for patients, rather than continually relying on the same standard methodology, every trial needs to apply the best science to clinical management – as we seek to do at GSK. This is a learning for both academia and industry, as both need to look at this gap and do better translation to bridge it.”

“Reverse translation, for example, is a hugely promising approach but there is still a lot of progress to be made in industry for it to be done well,” he continues. “Currently, if a drug fails at Phase 2 or 3, the whole program tends to be shut down to avoid further failure or financial loss. Often no or very little resource is spent on characterizing the patient population to explain why some respond and some do not – and to make predictions of patients for which treatment will be successful. I would argue that unless you learn from the reverse translation, you're not going to improve forward translation.”

Professor Ng also acknowledges that significant hurdles remain in closing the gap. Exploratory methods or biomarkers discovered in research require a host of approvals before they can be made part of clinical management. This is not easily achieved by academics, and so industry is needed to demonstrate that these new approaches meet the required regulatory standards – underscoring the need for a cohesive and multidisciplinary public–private relationship.

“At GSK, we’ve also invested a lot of effort to explore how we can make discoveries from patient samples and disease models such as patient-derived organoids into clinical biomarkers. As without a standardized test to identify patients who will benefit from an intervention, we may lose clinical impact for the research we do. This means creating strong relationships with collaborators from areas such as precision medicine – led by Anne-Marie Martin at GSK – to work together to translate findings into clinical biomarker development. It’s one of the last hurdles to overcome so that we can benefit more patients.”

Anne-Marie Martin adds: “The beauty of Tony’s work is that we now have better predictive preclinical models to help identify biomarkers that can be tested in the clinic. This will not only help us identify the right patient for our trials but should also increase our probability of success as we have a better a priori understanding of response and resistance, which will aid study design. This work is crucial for the Precision Medicine team that I currently lead, to bring forward the right hypotheses into the clinic which should help us drive better outcomes overall. Oncology Translational Research and Precision Medicine work ‘hand-in-hand’ and it’s this strong collaboration that will lead to the best outcomes for patients.”

As well as closing the gap between fundamental research and clinical care, Professor Ng recognizes the need of a more cohesive way of working in academia relative to industry. “There are lots of hurdles for multidisciplinary research in academia – hurdles as trivial as who deserves credit for a project, or who is first or last author on a paper and which discipline should take a more prominent position in the list. There is a lot to overcome but again sitting within GSK and KCL, I can see that we have the right tools to make an impact if we can all align and pull together to tackle these final barriers.”

A call for multidisciplinary action in oncology

Beyond gaining traction for the KCL- and GSK-developed approach in the clinical setting, Professor Ng also hopes to inspire a new generation of cancer clinicians and scientists to continue this work – “a generation that are younger and smarter, that can think of new ways to refine and sharpen the approach that we are developing,” he says.

“I started my research career doing science to extract the best possible insights from patient samples and soon realized that simplistic correlations were not enough. Beautiful science has been done in transgenic mice and other animals, where you can systematically knockout genes and demonstrate a causal relationship. But if you use the same approach in humans, you generate many different correlations. How can you identify which one is causal? Finding causality between parameters in a heterogeneous population, and turning those causal relationships into targets for patients who didn’t respond to chemotherapy or another drug, presents a great opportunity. But for this the field needs biologists and medics who can think quantitatively, or can collaborate effectively with quantitative experts. This requires a certain degree of understanding and respect for each other's discipline.”

As well as the joining of biomedicine and quantitative approaches, Professor Ng sees more active roles that bridge between the public and private sector as essential to progress in oncology. “As someone who has a clinical background, I benefitted from several research fellowships that allowed me to continue my research while still practicing as a physician. Even my early work in HIV, where I saw opportunistic cancers such as non-Hodgkin’s lymphoma and Kaposi sarcoma, was essential to the translational work I do now. Even though we’re now using cutting-edge science such as sophisticated scientific modelling, multi-omics and AI and mathematics; my earlier exposure to both fundamental research in biology and immunology paired with patient work in the clinical setting laid the foundation for what I do now.”

“However, my dual way of working is still relatively unique. When I transitioned from part time to almost full time in industry, I was only able to keep my professorship at KCL because it was supported by senior colleagues in the university and at GSK, and in the hospitals that we work with. That was a very rare opportunity as there are many conflicts created by its nature, but we need to make it a much more common pathway so that it is easier for others go down the same track.”

Barriers include IP concerns, the competitive nature of the environment, regulatory and compliance issues, resource allocation as well as other challenges such as cultural and organizational differences. Addressing these barriers often requires proactive efforts from both sides to establish mutual trust and clear agreements, which can take years of negotiation before any work is done.

“But when it can be done, it is hugely beneficial. It allows me to navigate many different components that are essential to the overall clinical developmental pathway – this includes both early research and the clinical setting, as well as biobanks, hospital systems and departments such as surgery, radiology and pathology, and components such as finance and legal. So, by coming into GSK, I could use my position to optimize the whole process of doing translation for patients. For instance, if we want to start a complex clinical trial with exploratory biomarkers in it, we need someone who can navigate that whole system and get multiple functions and disciplines behind that trial. This is what I could offer to GSK. I also know many of the hurdles that come up in this industry–academic interface that I could have only learned from my seven years of directing a cancer centre that sits between the hospital and university settings.”

As well as a more multidisciplinary approach, Professor Ng believes better communication between a broader set of stakeholders is needed. “In a country such as the UK, which is relatively small compared to other places like the US, China and the Middle East, more dialogue is needed between the government and industry, university and hospital stakeholders. This is the only way to work out the optimal model for more partnership and collaboration, so that we have access to the diverse populations needed to develop more innovative solutions and make better progress in cancer research.”

Through such efforts, Professor Ng believes that we have the ability to make real progress in the fight against cancer. “It's always been about the gap between the excellent fundamental science and the way we run clinical trials and manage patients. My whole purpose is to bridge that gap with equal cooperation from everyone involved. We need to bring the knowledge, network and execution together so that we can get ahead of cancer for the millions of people worldwide who are counting on us. There is more work to be done, but I believe we have what we need to move forward along this very exciting path.”