An Introduction to the Personalis Liquid Biopsy Approach

Kedar Hastak, MS, PhD
Manager, Field Applications Scientist

An Introduction to the Personalis® Liquid Biopsy Approach

As oncology technology continues to improve, there is an ever-growing buzz surrounding the topic of liquid biopsies. Just on its own, the concept itself is captivating: instead of having to take a physical sample of a patient's tumor or malignancy, doctors can simply take a sample of the patient's blood, urine, saliva, or spinal fluid to get a picture of what's going on.

And, since traditional biopsies can be painful, invasive, or dangerous in the most extreme of circumstances, it's no wonder that researchers and biotech companies are focusing on quickly developing and validating better liquid biopsy technology.

While it's important to keep in mind that liquid biopsies aren't the "silver bullet" that will render traditional biopsies obsolete, rather, new technologies can tell us more and more about cancers with minimal intrusiveness. Ease of use and data collection efficiency will only continue to improve, making liquid biopsies one of the most interesting areas of change in the field of oncology. Today, measuring molecular residual disease and tracking variants has immediate clinical utility (see our previous post on NeXT Personal™), but there is certainly more information about a patient's disease to be gleaned through liquid biopsy. As we learn more about the biology that's at play in a tumor, we can extend our understanding of these signals by interrogating them in blood.

Personalis' NeXT Liquid Biopsy™ approach builds on years of experience, technological advances in sequencing solid tumors, and analyzing the many facets of cancer biology including immune response, and moves this analysis into a non-invasive assay.

Typical Study Roadmap

Understanding the molecular profiles of a patient cohort begins by analyzing the biological signals present at the site of the solid tumor. Therefore, our process first begins with enrolling patients for characterization using our ImmunoID NeXT^® platform. ImmunoID NeXT is an advanced solid tumor biopsy test that analyzes exomes and transcriptomes from the patient's tumor. This more traditional biopsy analysis is usually only performed once (pre-treatment), and may be used to develop a clinical trial assay (CTA) on its own, or in tandem with our less invasive, liquid biopsy tests.

The breadth of data from the ImmunoID NeXT assay may be directly compared to the data collected from each time point analyzed using the NeXT Liquid Biopsy assay. When analyzed in concert with the solid tumor biopsy results, the overlap of information between the two gives a world-class picture of the cancer.

One advantage to the NeXT Liquid Biopsy test is that it may provide a more accurate picture of tumor heterogeneity. Assessing the level of a cancer's heterogeneity is essential to understand the results of a clinical trial, and can provide insights into future tumor mutations that may play a role in the trial readout or future drug developments. Each cancer has a unique and diverse collection of distinct molecular signatures, differing driver and passenger mutations, and biomarker statuses, all of which can provide clues about the lifecycle of the disease and opportunities for treatment. While the ImmunoID NeXT test gives a specific picture of a specific slice of the tumor, the NeXT Liquid Biopsy assay delivers a wider viewpoint, elucidating signals that a traditional biopsy might have missed.

The first NeXT Liquid Biopsy test and the ImmunoID NeXT test are taken at the same time point, giving the most full picture of the cancer, at the expense of a slightly more invasive process. After this first battery, sponsors can minimize invasiveness, while maximizing useful information collected throughout your study. From this point on, the study may include any number of subsequent NeXT Liquid Biopsy tests to complement this first snapshot of the cancer. These can be extremely useful for monitoring and exploring the cancer further, and can be also used to identify remission of the disease.

Figure 1:NeXT Liquid biopsy captures a robust picture of the myriad of signals present in the blood. When coupled with the ImmunoID NeXT tumor profile, a full picture of the patient's molecular profile is obtained.

Observing Intrinsic and Acquired Resistance

Liquid biopsies can serve other purposes as well, a central one being the observation of disease resistance to different treatment solutions, also important in understanding the outcomes of a clinical study.

As a patient receives treatment, the cancer can sometimes mutate to become more resistant to the drugs or radiation that once worked extremely well. In situations like these, it's important to know about these changes as soon as possible, to be best positioned to quickly pivot to a different course of treatment. NeXT Liquid Biopsy allows professionals an exome-wide view of the cellular variants of the cancer to immediately see how it reacts to treatment.

Studies have shown that in some cases where therapy produces "dramatic initial responses," many of these tumors develop resistance to the course of treatment. NeXT Liquid Biopsy can provide information on both common and novel treatment-resistance pathways that often develop over time, allowing analysts to get a better idea of what kind of mutations can lead to future resistances.

Casting a Wide Net: Looking For the Macro As Well As the Micro

Importantly, Personalis' NeXT Liquid Biopsy approach goes beyond traditional liquid biopsy approaches that look primarily at targeted panels of genes. While employing a traditional methodology that targets a specific genomic footprint works well to analyze those well-known genes, a wider genomic picture can deliver crucial information. Personalis' approach aims to capture a more global understanding of the tumor dynamics at play, delivering more useful data for your study and enabling the discovery of biomarkers that may improve outcomes.

NeXT Liquid Biopsy captures all ~20,000 protein-coding genes in the human genome, allowing for a widened viewpoint. Taking multiple liquid biopsy tests over the course of your study allows Personalis to look for irregularities between genes that many other tests don't sample at all. This allows for a high level of personalization, allowing your team the best chance of noticing something that another test might have missed. This is the heart of the Personalis NeXT Liquid Biopsy approach: casting a wide net of signals characterized during your clinical study to enable more impactful treatments and care paths.

Contact us to learn more about NeXT Personal and NeXT Liquid Biopsy.

All products described here are for Research Use Only and not for use in diagnostic procedures (except as specifically noted).