Philip Beer, Chief Scientific Officer at Step Pharma, stressed the need to explore the importance of ctDNA in drug development and genomic reporting, especially in clinical trials. While there is a lot of excitement around ctDNA there are multiple difficulties with ctDNA in the clinic in an actual real-world setting. The main challenge hindering the wider adoption of liquid biopsy in clinical settings is funding and reimbursement. Additionally, there is a demand and pressing need for better evidence of clinical utility to justify the costs.
Beer stated that liquid biopsies fall into four key categories: early detection, diagnosis, treatment response, and disease progression. Beer’s talk focused on their applications in the areas of diagnosis and disease progression.
When using liquid biopsies at diagnosis the core limitation around using ctDNA analysis at diagnosis is reduced sensitivity which enhances the risk of false negative results. This is attributed to low shedding tumours.
Alongside this, clonal haemopoiesis which can mimic tumour mutations adds additional complications. Beer also said: “There are also particular difficulties in certain types of variants, particularly deletions where ctDNA is suboptimal.” To prove this point home, Beer presented a few case studies that proved that ctDNA results were ambiguous or confounded by blood-derived mutations in pancreatic and lung cancers.
However, Beer emphasises that ctDNA is particularly valuable for disease progression. Unlike single-site biopsies, liquid biopsy can capture tumour heterogeneity and emerging resistance mutations across multiple tumour sites. Examples include resistance mechanisms in breast, ovarian, and cholangiocarcinoma patients, where ctDNA revealed actionable mutations that could guide therapy adjustments.
So, what can be done to tackle these barriers and increase the uptake of ctDNA in the clinic? Beer’s main suggestion is to implement a more targeted use of ctDNA by prioritising its role in monitoring disease progression and resistance rather than as a primary diagnostic tool. He also advocated for centralising genomic labs to streamline workflows. With coordinated efforts and infrastructure in place, liquid biopsy could fully realise its potential in oncology.
