Written by:
Vice President, Translational Medicine, Oncology R&D, AstraZeneca
Vice President, Cancer Biomarker Development, Oncology R&D, AstraZeneca
What is meant by translational science?
Translational science is the process of translating research discovery into actionable insights in the clinic, while leveraging clinical data for further discovery to benefit patients. At AstraZeneca, translational science plays a pivotal role in developing precision medicines, acting as the link between early scientific breakthroughs, their application in clinical decision making and the development of next generation diagnostics. This rapidly developing field is expanding our knowledge of tumour biology, pioneering state-of-the-art biomarkers, and informing the design of innovative clinical trials which have the potential to transform outcomes for patients.
Addressing differences in patient responses to cancer medicines
The varied responses that patients have to medicines make it challenging to develop new treatments that work for everyone. Despite sharing the same cancer diagnosis, each patient has a unique molecular profile that influences their response to therapy. These differences, arising from variations in their genetic make-up, tumour mutational status, target expression, epigenomics and more, are complex and have shifted the focus of research and development toward precision medicine.
In furthering our understanding, translational science plays a key role in decoding which patients are likely to respond to treatment, what factors contribute to their response, and what we can learn about the drug mechanism of action in the process. One way to approach this is to observe patient response to treatment and seek novel mechanistic insights. For example, elimination of malignant cells during treatment represents an important moment for recovery but also provides valuable insights into how their unique molecular profile responded to treatment.
However, accurately assessing and predicting this is challenging. Traditional methods rely on post-surgery microscopic examination of tumour tissue, a process prone to overlooking residual cancer cells. The future of improving assessment and shaping the precision medicine landscape relies on translational science and innovative clinical trial design.
What is the role of translational science in research and development?
Translational science has a critical role in accelerating clinical decision making, providing insight to mechanisms of response and resistance, and advancing our understanding of how to target early disease. By developing more accurate predictors of treatment response, we unlock clinical innovation and inform the next wave of therapies.
At AstraZeneca, we are accelerating innovation by bridging the gap between early discovery, biomarker identification and clinical practice, to inform the development of next generation diagnostics which have the potential to improve patient outcomes.
Through close collaboration with our Cancer Biomarker Development team, we are identifying novel predictors of treatment response, with the aim to select and treat patients earlier, minimise unwanted effects from treatment, and help design innovative clinical trials based on rigorous science.
Innovative translational technologies
As we delve deeper into the complexities of tumour biology, the volume of data generated with cutting-edge technologies is empowering us to interrogate tumours with unprecedented precision. This more granular understanding is fuelling the development of next-generation diagnostics and transforming clinical decision-making.
Revolutionising target quantification with AI
At the forefront of this transformation is computational pathology, which harnesses the power of artificial intelligence (AI) to analyse tumours at a level of precision, accuracy and reproducibility that was previously unimaginable. One such method, developed by our teams, is Quantitative Continuous Scoring (QCS).
QCS looks for the presence or absence of a biomarker, quantifies its location in sub-cellular compartments, such as the membrane, cytosol and nucleus, and analyses the biomarker in the context of the broader spatial organisation of the tissue. It is becoming invaluable for understanding the mechanism of action of targeted therapies, such as antibody-drug conjugates, and for identifying patients who are most likely to benefit from treatment. We are in the process of embedding QCS into our portfolio, with the goal of gaining regulatory approval as a first-in-class set of computational pathology AI-driven predictive biomarkers.
Higher-definition multimodal biomarkers
We are also spearheading the development of multimodal biomarkers through deep multiomic analysis, integrating molecular, genetic and imaging data. These comprehensive biomarkers aim to simplify and streamline clinical decision-making by leveraging multiple elements of disease at a molecular level.
Biomarkers are molecular signposts, which guide scientists and clinicians through the intricate complexities of the landscape of cancer, revealing hidden pathways and providing crucial clues to its dependencies and vulnerabilities. These markers are essential in transforming our understanding of tumour biology into benefit for our patients. We depend on them to identify the right target, the right treatment for the right patient at the best stage of their therapeutic journey
Unlike traditional biomarkers, which typically assess only a single variable, multimodal biomarkers provide a panoramic view of the disease, enabling an integrated approach to diagnosis and treatment. This allows us to better define treatment strategies tailored to each patient's unique tumour profile. These approaches are central to our trials, and a critical way in which we follow the science to inform clinical decision-making.
We can also track tumour dynamics through blood based ctDNA profiling to help us understand the differences in how patients respond to treatment. We are routinely including ctDNA analysis as a secondary endpoint in many of our clinical trials and to monitor minimal residual disease after surgery. Non-invasive ctDNA analysis is changing the way in which cancer is detected, treated and monitored, providing predictive insights on patient selection and drug resistance to inform precision medicine strategies.
Answering translational questions through innovative trials
The insights derived with transformational technologies, such as ctDNA profiling, computational pathology and deep multiomic analysis, are revolutionising not only diagnosis and prognosis but also clinical trial design. To harness novel insights, we are designing our trials to strategically address translational questions, with the aim to maximise benefit for patients.
For example, by collecting tumour samples before, during and after treatment, we can achieve a better understanding of tumour dynamics. This includes "window-of-opportunity” studies which focus on the time between diagnosis and the initiation of treatment when tumours remain untouched by therapy and present an opportunity to study the molecular characteristics that define cancer cells.
In this way, innovative clinical trial design allows us to identify biomarkers, genetic mutations, and other factors that inform rational treatment decisions and contribute to the ongoing development of more personalised and effective therapies.
Poised for deeper impact
Our academic backgrounds ignited a shared passion for decoding the secrets of cancer biology. At AstraZeneca, we are dedicated to nurturing this passion through close collaboration with our world-class colleagues and the wider biopharmaceutical, academic, regulator and clinical communities.
Translational science is at the heart of the revolution in oncology research and development, positioned as a catalyst for discovery in the laboratory and the clinic, and underpinning the development of next generation diagnostics and predictive biomarkers. Our progress will be defined by our ability to reshape our understanding of tumour biology, reliably predict treatment response and resistance, and find new ways to attack cancer from multiple angles.
Join us as we continue to look for ways to make a difference to patients
We welcome committed, talented scientists to join us on what promises to be one of the most exciting, stimulating and rewarding journeys in 21st century medicine.
A leader in oncology with a global footprint, we are growing a differentiated pipeline to address a range of tumour types associated with significant unmet need. There are limitless opportunities to make your mark, take smart risks and pioneer new ideas. Diverse in experience and approach, our team shares a passion to follow the science and bring life-changing medicines to people across the globe.
We recruit scientists with relevant expertise to join us in our state-of-the-art facilities in Barcelona, Spain and Gaithersburg, US.
