Elizabeth Harrington delivered a comprehensive overview of the role of biomarker research in the development of new cancer therapies, drawing on her experience as Executive Director at AstraZeneca.
Harrington began by outlining the three pillars of translational medicine that underpin the implementation of biomarkers in novel trial design. The first pillar focused on understanding the impact of new molecules on tumours and their microenvironment, ensuring the selection of appropriate doses and schedules, and evaluating mechanisms of action to guide combination therapies.
The second pillar emphasised the identification of the right patients for specific therapies, using predictive biomarkers to determine likely responders and those with innate resistance, thereby informing the development of companion diagnostics and early response markers.
The third pillar, termed ‘back translation’, involved learning from clinical experience – particularly mechanisms of acquired resistance – to inform the design of new therapies and rational combinations.
Harrington illustrated these principles through three case studies. The first concerned PARP inhibitors, where she explained how understanding DNA repair pathways and BRCA mutations enabled the selection of suitable patients and the design of effective clinical trials. The development of pharmacodynamic biomarker assays, such as the PARylation assay, allowed for precise measurement of drug activity in both blood and tumour samples, supporting dose selection for advanced trials.
The second case study focused on selective oestrogen receptor degraders (SERDs) in breast cancer, highlighting how resistance mutations in the oestrogen receptor gene ESR1 emerge during treatment. Harrington described the use of circulating tumour DNA to monitor these mutations and the innovative trial designs that now allow for early intervention with novel therapies like camizestrant, potentially extending the benefit of first-line treatments.
The final case study addressed EGFR inhibitors in non-small cell lung cancer, demonstrating how the identification of resistance mutations and the use of response markers such as circulating tumour DNA inform both patient selection and the development of new combination therapies.
Harrington concluded by emphasising the ongoing importance of spatial biology and digital pathology in refining biomarker strategies, and the potential for these advances to drive the next wave of cancer therapy innovation.
