Technology Networks Feature: How Protein Mapping Could Transform Target Discovery in Precision Oncology

Q: Sapient recently launched the Tumor Protein Mapping Platform. What gap in oncology research or drug development does this tumor proteomics platform address, and why has it been so difficult to tackle until now?

A (Jeramie Watrous): The efficacy of most oncologic therapeutics is determined by their interaction with a target, typically a protein within the tumor. The therapeutic either binds that protein and allows a payload, such as a chemotherapy, to enter the tumor cell, or inhibits a fundamental process essential to the tumor’s survival.

The real challenge is identifying the best proteins to target for next-generation therapeutics. An ideal target is one that is highly expressed in cancerous tissue but present at very low levels in normal tissues. This differential is what gives rise to the therapeutic index: the dosing window within which a drug can selectively affect the tumor without harming healthy tissue.

To date, identification of such differentially expressed targets has been heavily dependent on genomics measures: DNA and, increasingly, RNA through bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics.

The challenge is that this data is largely inferring protein levels. We know that protein abundance and activity can shift independently of RNA due to post‑transcriptional regulation, alternative splicing, protein degradation and localization, and post‑translational modifications—meaning that in reality, RNA and protein levels are often poorly correlated.

RNA may suggest that a particular gene product represents a great target, but when we look at actual protein levels, that is not the case. The reverse is also true: RNA can miss a substantial number of targets where the differential expression appears minimal at the transcript level but is actually quite significant at the protein level.

What has now changed is our ability, for the first time on both a technological and scientific level, to assay proteins at scale directly in human tumors and tissues—whether fresh-frozen or FFPE samples—on the order of 10,000–12,000 proteins per sample with advanced tumor proteomics platforms.

We can also localize them to specific regions of the tumor cell, such as the cell surface, and identify proteoforms that contain therapeutically relevant epitopes. This enables us to identify new targets and assess their validity in a more direct and comprehensive manner, improving target selection up front, which in turn improves the overall probability of success in drug development.

Q: How important is it to analyze surface biology, signaling, immune context, and resistance mechanisms together rather than as separate datasets?

A (Jeramie Watrous): It fundamentally depends on the underlying biological question being asked. There is no single “best” tool for all experiments, and I believe a large portion of experimental failures stem from an improperly scoped study rather than technical limitations.

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