“Genes don’t reliably predict response to treatment, and the gene mutations or expression in cells don’t reliably predict the expression of proteins in our cancer cells… If we ever want to achieve precision oncology, we must figure out both on the science side and on the institutional side how to embrace diagnostics of many proteins, coupled with some genes or gene expression, and patient data.” – Amanda Paulovich
A panel of experts in proteomics: Karin Rodland, PhD, (Pacific Northwest National Lab and OHSU), Amanda (“Mandy”) Paulovich, MD, PhD, (Fred Hutch), Kristina Beeler, PhD, (Biognosys, which provides proteomics services to biopharma), and Marlon Ruiz and Michael Förster, PhD, (Olink, which offers a proteomics platform to scientists), discussed the role of proteomics in clinical decisions.
1. Where are proteomics as an emerging technology?
Amanda Paulovich: Mass spectrometry has proven to be a reliable measure of proteins, which can be combined with genomics to offer clinical insights through laboratory-developed tests. The challenges now are (a) clinical translation from a laboratory environment to a regulatory environment meeting FDA approval, such that pharma will begin to adopt it in its late phase trials, potentially leading to companion diagnostics; (b) increased reimbursement for diagnostics in general, and for mass spectrometry specifically, so that laboratories that provide the service can stay afloat; and (c) increased physician uptake.
Kristina Beeler: The applications of our proteomics technology when we started a decade ago were in small scale studies answering basic research questions for our biopharma customers. In the last seven or eight years, we’ve seen a push for the technology to be adopted much later down the drug discovery pipeline. We’ve seen the adoption of the technology in preclinical settings to understand the mechanism of action in drugs to identify novel drug targets. Now, clients are waiting for the data to make decisions on the next cohort enrollment. This is something that we could never have imagined a few years ago. This is still in a clinical trial setting. Taking that to the next step is still quite a way down the road.
Karin Rodland: We’re at the stage of developing tools to combine genomic, mRNA, and proteomic data to improve the selection of likely therapeutic drugs that you will respond to.
2. How are proteomics helping guide treatment decisions – what is distinctive?
Michael Forster: Proteomics have the ability to monitor proteins and biology and cancer-related changes in real time. The biomarker information you derive in real time is closer to the therapeutic intervention, enabling you to gear therapies better to specific patients.
3. How should proteomics be integrated with other diagnostic tests to guide clinical decisions?
Karin Rodland: If I was doing an N-of-1 research experiment on Brian, I would take his RNA-seq data and the biological processes that had been implicated, and I would use Mandy’s targeted proteomic assays, and I would verify which kinases in that pathway are actually upregulated and driving the abnormal behavior in the pathway.
4. What’s next?
Kristina Beeler: Complex biological processes are characterized not by just one level of -omics. They need the multi-omics level and current status. Proteins provide essential functional information to understand the true phenotype.
Karin Rodland: Looking at Brian as a research project, how do we make proteomics available to him as a research subject? He has to find a physician and a precision oncology clinical trial to look at all these different molecular measurements and integrate them and get enrolled. Then we will need to address the question that Mandy is trying to focus on: “how do we turn that into the standard of care?”
Amanda Paulovich: You really need partners in large academic centers that are willing to go out on a limb, and centers that are legally adventurous enough and willing to go down that path with you. Unfortunately, it’s just hard to do. As Karin said, you’re pushing the envelope beyond what standard of care is.
We need better diagnostics. 80% of healthcare decisions are based on diagnostic tests, but they account for less than 20% of healthcare costs. Somehow, diagnostics must be valued in the same way that blockbuster drugs are, and they’re way way undervalued right now.