Proteomic Liquid Biopsies Could Expand Early Breast Cancer Detection and Precision Oncology Strategies

In this interview with Pharmacy Times ahead of the American Society of Clinical Oncology Annual Meeting (ASCO), Jayant Parthasarathy, PhD, CEO and cofounder of Astrin Biosciences, discusses the broader vision behind Astrin’s Certitude platform and its potential role in advancing precision oncology through plasma-based proteomic testing. Parthasarathy explains why the company prioritized proteomic profiling over genomics, particularly for cancers such as breast cancer that may not shed enough circulating tumor DNA for reliable genomic liquid biopsy detection. He highlights how deeper proteomic analysis could help identify cancers earlier in patients with dense breast tissue, monitor recurrence, and potentially inform targeted treatment selection. Parthasarathy also discusses emerging applications for oncology pharmacists, including biomarker-driven therapy monitoring, longitudinal assessment of treatment response, and integration of proteomic assays into personalized cancer care strategies.

Pharmacy Times: Can you talk about the broader vision for the Certitude platform and where you see it fitting into the future of precision oncology and cancer diagnostics?

Jayant Parthasarathy, PhD: We began Certitude by trying to solve a problem that has eluded liquid biopsies for a long time: finding the earliest signals of breast cancer. The focus for Certitude was to serve a significant unmet need, as more than half of women in the country and around the world have dense breasts, where mammography is not as sensitive.

We asked whether liquid biopsies could serve as a medium to identify these signals as early as possible, not just among the broader population but also among younger women, where we are starting to see a greater rise in the incidence of breast cancer. Conventional imaging has had challenges in this setting, and genomic-based liquid biopsy tests have had similar limitations, particularly because early-stage sensitivity has not been what we would like it to be.

Our approach was based on the idea that signals beyond the genome exist in the bloodstream. If you are able to build a platform that can see deeply enough and be sensitive enough, then you are going to be able to pick these signals up. For us, that meant looking at functional molecules and proteins that serve as a medium of exchange between the cancer cell and the host through biologic crosstalk. If we are able to tap into that crosstalk, we believe we can identify some of the earliest signals of breast cancer.

Breast cancer is one of the toughest cancers to detect in the bloodstream, and solving for that challenge allows us to branch into other cancers where there is a similar unmet need. Our vision for Certitude is to someday solve for some of the toughest cancers that are difficult to find through imaging or other liquid biopsies, detect them as early as possible, and potentially utilize that information to monitor individuals for future signs of recurrence.

Beyond detection, we also see an advantage in looking at proteins because it may help us learn how best to target some of these cancers. Could there be targeted therapies that could be employed, and if so, which one might be the most effective?

Broadly, there is a 2-part vision for Certitude. The first begins with early breast cancer detection, specifically for women with dense breasts. The second is growing into a combinatorial product that can also help identify the best treatment modality for that individual patient.

Pharmacy Times: Many liquid biopsy approaches today focus heavily on genomics. Why was it important for Astrin to focus on proteomic profiling, and what additional insights can protein expression provide for oncology teams?

Parthasarathy: This goes back to the significant amount of work that has been done in liquid biopsies looking at the genome, epigenetic factors, and methylation. Certain cancers shed sufficient DNA material into the bloodstream, while others do not. Breast cancer is a good example, as it does not shed enough material into the bloodstream to be reliably detected by genomic technologies.

Because of that, we had to solve the problem using an entirely different paradigm. We believed that signaling beyond the genome existed, and that the key was identifying the deep proteomic signature that defines early onset disease. The challenge with proteins has always been that, although these signals have long been hypothesized to exist, the question has been whether technology could see deeply enough to detect them.

There are approximately 10,000 to 12,000 proteins in the bloodstream, and a small handful account for 99% of the entire proteome in terms of abundance. To see deeply enough required a platform and technology that took a completely different approach from what had been done previously. That is what this team has built: the ability to see deeper than ever before and, in doing so, identify cancer signatures that would otherwise be missed by genomic technologies.

Breast cancer is a perfect example. It is the most prevalent cancer among women and perhaps the largest cancer globally from a volume standpoint. For nearly half of women, imaging technologies such as mammography will miss these cancers early. For us, the goal was to employ proteins and proteomic technologies to address that major unmet need.

Pharmacy Times: As more targeted therapies and radioligand treatments enter oncology, what role do you see pharmacists playing in the integration of plasma-based proteomic testing into routine cancer care?

Parthasarathy: One of the major achievements in recent years has been demonstrating that proteomic signals identified through liquid biopsies can be comparable to what is found in tissue biopsies. For example, in situations where it is difficult to access tumor tissue or biopsy an individual, liquid biopsies could serve as a valuable tool, particularly in the targeted therapy space, to help identify the best therapeutic approach for a patient.

We also believe liquid biopsies could play an important role in monitoring patients longitudinally to determine whether a therapy is working and, if it is not, what the next best step or action might be. Our vision, based on work we recently presented ahead of ASCO, is to develop a panel of proteins linked to specific targeted therapies that can quantify longitudinally the presence, absence, and extent to which these targets are visible in plasma.

By correlating these findings with treatment outcomes, we may be able to identify opportunities where a particular target begins to express itself while others do not and then use that transition to help guide treatment decisions. Similar to how liquid biopsies have guided genomic-based therapies, we ultimately see an opportunity for liquid biopsies to guide protein-based therapies as well. That is why we believe platform selectivity offers such a significant advantage.

Pharmacy Times: Oncology pharmacists are increasingly involved in biomarker-driven treatment selection, monitoring, and patient education. How could tools like Astrin’s proteomic assay help pharmacists better identify patients who may benefit from specific targeted therapies or require closer monitoring throughout treatment?

Parthasarathy: We are working with several groups across the country to answer exactly that question. Oncology pharmacy teams are collaborating with us to monitor individuals through panels of proteins as they undergo specific treatments and to better understand whether those treatments are having an effect on those protein profiles.

If, for some reason, a treatment is not producing the result we would like to see, we are exploring how those findings could help guide a transition to a different therapeutic approach. We believe oncology pharmacists, and the oncology care team in general, are at the forefront of implementing newer technologies such as proteomics in the clinic to better serve patients.