The Coming Shift from Biomarkers to Biological Trajectories

The traditional approach to medicine has long viewed disease as a static condition, with diagnosis, treatment, and monitoring focused on identifying a single biological state. However, this perspective fails to capture the dynamic nature of biological processes. Disease is not a fixed point, but a continuous journey shaped by the interactions of cells, tissues, and the immune system, along with environmental factors and therapeutic interventions.

In recent years, there has been a growing recognition that a more fundamental question arises: What is happening inside the cell that leads to the detection of disease-associated biomarkers in the blood? While existing measurement tools have been effective in detecting specific markers such as mutations, proteins, and lesions, they provide only static snapshots of biological systems.

They reveal what is present at a given moment, but do not capture the dynamic changes, reasons behind those changes, or the future direction of the biology.

The evolution of liquid biopsy has been instrumental in advancing this understanding. Originally, liquid biopsies focused on detecting disease-associated DNA in a patient's blood. Subsequent generations expanded to sequence the DNA, identifying cancer-associated mutations, monitoring molecular residual disease, and inferring the tissue of origin. However, these approaches still emphasize what is present and where it comes from, rather than understanding the functional state that generated the signals in the first place.

To truly transform medicine, we need to move beyond measuring static biological signals and begin to measure the biological processes that produce those signals. Disease often arises from the coordinated actions of multiple cell types, such as tumor, stromal, and immune compartments. Understanding these interactions and transitions between biological states requires new measurement tools that can capture the functional information present in circulating biomarkers.

This shift towards "trajectory medicine" involves measuring the dynamic biological processes underlying disease, rather than simply identifying static states. By monitoring the trajectories of biological states over time, clinicians can gain a more comprehensive understanding of how a patient's condition is evolving and respond to treatment.

This approach has the potential to revolutionize care for a wide range of diseases, including rheumatoid arthritis, oncology, inflammatory bowel disease, fibrosis, neurodegeneration, and transplantation.