The power and promise of liquid biopsies

Tumor tissue diagnostic biopsies are a critical component in cancer care. These valuable samples confirm whether a patient has cancer, provide a snapshot of the tumor-host microenvironment, and help determine a malignancy’s potential aggressiveness. Digitized pathology images and advanced analytics offer even more information from biopsies, especially when histological data is complemented with targeted molecular information through immunohistochemistry (IHC) and other means. Add in next generation sequencing (NGS), which provides comprehensive molecular insights, and the information from biopsies further improves risk stratification, identifying specific mutations and genomic markers that can predict therapeutic benefit.

Still, surgical biopsies have their drawbacks. First, they are invasive. We think of biopsies as relatively minor operations, but such procedures can be serious. As a result, biopsies can be challenging to perform, and repeated biopsies over time to monitor cancer progression and optimize therapies are seldom feasible. We usually get an initial diagnostic biopsy and, sometimes, a second upon spread or progression.

Even when accessible, any single biopsy sample may not represent an entire tumor due to cancer heterogeneity. Mutations can be localized to different regions, and tumors often include varied proportions of different clones. One tissue sample from a single region will rarely capture the full complexity of an individual’s cancer.

Even with our incredible tissue biopsy analysis advances, accessibility challenges and tumor heterogeneity demand complementary solutions to evaluate tumors more frequently and comprehensively.

That’s why many, including myself, are enthusiastic about liquid biopsies, which can provide crucial molecular information with simple blood draws. As cancers grow, they slough off cells, cell fragments, and DNA from apoptotic or necrotic cancer cells, which enter the blood stream and offer tremendous opportunities to better assess cancer.

Though we’re only beginning to understand how to use this information to optimize patient outcomes, blood samples are already outlining cancer aggressiveness, identifying treatment options, tracking efficacy, and precisely managing each patient’s unique disease.

As NGS costs decrease, and our understanding of cell-free RNA, circulating tumor cells and exosomes increase, these diagnostics will provide even more powerful information to guide treatment.

Our current focus on targetable mutations will soon include genome-wide signatures, such as DNA repair issues and epigenetic markers, which can provide additional information to describe a cancer’s tissue of origin, metastasis location and other key metrics.

Because liquid biopsies interrogate cell-free DNA (cfDNA) from an entire tumor (or tumors), rather than a single tissue sample, they can provide more comprehensive information about their makeup to more fully capture mutational complexity.

Single-cell analyses will help identify clonal populations, and can find commonly shared cancer-driving mutations as well as collections of variants that represent most clones in order to enable highly effective, bespoke immunotherapies.

In the near future, cfDNA will help us refine a patient’s risk of recurrence and detect recurrence earlier than radiology. While some are appropriately skeptical that earlier recurrence detection will benefit patients, I am quite bullish. As more effective therapies emerge, our ability to treat recurrent disease earlier will translate into improved outcomes. I predict we will see a growing number of clinical studies to test this optimism.

As we make progress towards using liquid biopsies to better manage patients with later-stage cancers, we are simultaneously developing tests that detect tumors during their earliest stages, when they are most treatable. In this vision, liquid biopsies could be part of a standard annual physical, like cholesterol and blood glucose tests.

While screening success requires strong evidentiary support, success would shift the stage at which patients are diagnosed. More people will be diagnosed at stages 1 and 2 – while the objective is treatment for cure – rather than stage 3 or 4. Stage migration in ovarian, pancreatic, lung, and other cancers would result in improved outcomes.

Liquid biopsies will continue to advance. In the near future, we will move from single-sample analyses that provide only one, transitory snapshot of a tumor’s progression, to longitudinal studies that track cancer over time. This technology, combined with targeted therapies, immunotherapies, and other emerging approaches, will ultimately help us cure many patients.

Read about Illumina's new liquid biopsy and high-throughput assays in the TruSight portfolio here.