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The Next Generation Sequencing Advances Liquid Biopsy Companion Diagnostics for Precision Oncology

 The recognition and advancement of precision oncology are heavily attributed to cancer genomics that can provide cancer molecular information, allowing researchers to tailor treatments and improve the outcome for a spectrum of cancer and other indications. To realize the promise of precision oncology, researchers take efforts to identify and discover relevant biomarkers using genomic profiling, either for functional, diagnostic, predictive, or prognostic purposes.

 

The FDA's approval of two companion diagnostics (CDx)—the Guardant360 CDx assay and the FoundationOne Liquid CDx test in 2020 led the testing of multi-gene mutations and biomarker profiling to a new level. Prior to the approval of these two companion diagnostics that involve a combination of liquid biopsy and next-generation sequencing (NGS) technology, researchers had been stuck with the low meaningful mutation frequency and the difficulty in finding biospecimens with specific mutations.

 

Tumor characterization has been using tissue biopsy samples until the liquid biopsy appeared. Liquid biopsy, as an alternative to tissue biopsy, can count and analyze circulating tumor cells (CTCs) which are sloughed off from solid tumors into bodily fluids as biomarkers and could develop into metastases. Therefore, liquid biopsy is likely to reflect all invasive tumor subclones existing at a specific time point, allowing researchers to sequentially and longitudinally monitor the evolutionary dynamics of a tumor.

 

Increasing studies have evidenced that liquid biopsy has a potential for capturing tumor heterogeneity and is able to detect residual disease, recurrence, and even early signs of therapeutic resistance. Since biomarkers in bodily fluid samples like blood can be collected in a minimally invasive way, a CDx assay with liquid biopsy is generally defined as an informational in vitro diagnostic (IVD) device for more secure and effective application of a targeted therapeutic product.

 

As a whole, the clinical utilization of liquid biopsy companion diagnostics is promising in terms of the following advantages:

 

l Easier and more flexible sample collection compared with tissue biopsy.

l Lower risk of adverse reactions to therapeutic drugs or biological agents.

l Ability to perform serial testing with less invasion and higher frequency.

l Being a complement to tumor tissue and an alternative to tissue biopsy.

l Allowing for gene expression profiling at the single-cell level and other downstream analyses with cellular contents preserved.

 

To satisfy the need for biospecimens with a mutation of interest and advance the development of biomarkers across cancer indications, a project that performs mass screening of liquid biopsies taking advantage of NGS techniques and panels has been launched. By partnering with diagnostic developers, this project is expected to establish a database of NGS profiles, advancing the development of the next-generation diagnostics based on both tissue and liquid biopsy for precision oncology.

 

The next-generation sequencing technology helps identify genetic variations in tumor and non-solid biological tissue. A combination of NGS and liquid biopsy companion diagnostics allows scientists to analyze not only CTCs but also circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), soluble proteins, and exosomes, which helps understand the mechanisms of cancer development and progression, uncover potential drug targets, and discover novel biomarkers.

 

Except for the NGS technique, strategies for CDx tests include PCR, RT-PCR, expression arrays, fluorescent in situ hybridization (FISH), mass spectroscopy, Immunohistochemistry (IHC), etc.

 

It's acknowledged that high-quality and well-characterized biospecimens are powerful building blocks for the research of disease drivers, drug targets, and novel biomarkers. Genomic profiling programs are positively impacting the development of precision oncology. The liquid biopsy companion diagnostics using the next-generation sequencing techniques help enhance diagnosis, prognostication, and outcomes prediction for precision oncology. Integration of multi-omics tumor characterization and dynamic assessment of liquid biopsy samples is expected to be used for stratifying treatment and monitoring therapeutic response.

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