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The promise of precision oncology is being realized, with an array of targeted treatments and immunotherapies now available across a spectrum of cancer and other indications. Genomic insights have played a critical role in advancing our understanding of cancer biology and driving the development of precision therapeutics. Using tumor genomic alterations to predict therapeutic benefit from targeted therapy has improved clinical outcomes in a range of neoplasms.1, 2, 3 Given this success, there is increasing interest in using genomic profiling to inform and accelerate biomarker-driven research and development.

Recognizing the Value of Next Generation Sequencing

Next generation sequencing (NGS) helps pinpoint genetic variations in tumor or non-solid biological tissue, providing a window into the mechanisms of cancer development and progression and uncovering potential drug targets. A growing body of evidence supports the clinical utility of NGS. A recent study showed that, among 1,015 patients who participated in the Michigan Oncology Sequencing Program, 80% were found to have potentially actionable genomic alterations. Of the 132 patients who were given sequencing-directed therapy, over 37% experienced some clinical benefit and nearly 20% demonstrated exceptional responses.4 NGS was also able to decipher the tissue of origin in 50% of patients with cancers of unknown origin. Moreover, potentially inheritable cancer risk was identified in 16% of patients, raising the possibility of downstream benefit for family members with the same mutations.

The challenge for researchers and diagnostic or therapeutic developers, however, is that clinically meaningful, actionable mutations occur at very low frequency and finding biospecimens with those mutations is difficult. To take on this challenge, Precision for Medicine, Biospecimen Solutions is announcing an expansion of it’s Precision Oncology Sequencing Initiative (Project P.O.S.I.) to include Liquid Biopsy.

Rob Fannon, MPH, MBA
Rob Fannon, MPH, MBA
General Manager, Biospecimen Solutions, Precision for Medicine

“Sourcing high-quality, well-characterized biospecimens with a mutation of interest can be a Herculean task,” said Rob Fannon, General Manager of Precision for Medicine, Biospecimen Solutions. “Our vision is to create a library of deeply-phenotyped, data-rich samples that researchers can leverage to move precision medicine forward more quickly and efficiently.”

Advancing Biomarker Development with an Ambitious NGS Initiative

In partnership with a variety of diagnostic and pharmaceutical researchers, Precision for Medicine has launched Project P.O.S.I, a large-scale, two-phase next generation sequencing (NGS) initiative to screen samples in its extensive biorepository for key biomarkers across cancer indications. The first phase of this undertaking, which is ongoing, focuses on NGS screening of the company’s formalin-fixed, paraffin-embedded (FFPE) tumor tissues. Thousands of FFPE samples have already been screened on the Ion Torrent Genexus System with the Oncomine Precision Assay, which is designed to detect 2,768 unique cancer driver variants across 50 genes.

“With this NGS initiative, our biospecimens have become powerful building blocks for exploring disease drivers, drug targets, and novel biomarkers,” said Fannon.

The second phase of this initiative is focused on performing mass screening of liquid biopsies using a variety of NGS techniques and panels. Blood-based biomarkers offer flexibility, as samples can be collected less invasively and more frequently than tissue biopsies, enabling longitudinal assessments. Liquid biopsies may also be useful as a complement to tumor tissue, as analysis of both may provide additional insight into tumor heterogeneity and support therapeutic development.

Partnering with Diagnostic Developers

Pillar Biosciences (Pillar) has partnered with Precision for Medicine on this liquid biopsy NGS project, with the goal of accelerating development and advancing cell-free DNA (cfDNA) diagnostics. Pillar recently received FDA Premarket Approval (PMA) for its oncoReveal™ Dx lung and colon cancer assay, an NGS tissue-based companion diagnostic (CDx) intended to be used on the Illumina MiSeqDx®. Notably, this PMA CDx approval was the first among Illumina’s in vitro diagnostic (IVD) partners.

Precision for Medicine has created a global network that is actively collecting cfDNA from liquid biopsies obtained from patients with cancer. As part of this partnership with Pillar, these cfDNA samples are processed and sequenced using Pillar’s NGS workflow, which utilizes amplicon-based target enrichment technology. The resulting data is combined with key clinical information and liquid biopsy metadata for flexible, concurrent review and interrogation using QuartzBioSM, Precision for Medicine’s proprietary mulitomic data processing engine. This computational biology-enabled, AI-driven platform is designed to find relationships among diverse biological data.

“Our partnership with Precision for Medicine is enabling us to build a database of NGS profiles that will help accelerate discovery of clinically meaningful biomarkers and development of liquid biopsy-based diagnostics for precision oncology,” said Zhaohui Wang, Ph.D., Co-founder and Chief Scientific Officer at Pillar Biosciences.

As a specimen provider affiliated with an extensive network of patients and clinicians and a large network of specialized labs, Precision for Medicine also offers prospective collection capabilities and is uniquely positioned to support diagnostic and CDx developers.

“This initiative is agnostic to technology, platform, and analyte,” added Fannon. “Our goal is to help researchers and therapeutics companies develop their biomarkers and companion diagnostics. By enabling them to generate data from real clinical samples, rather than contrived specimens, we support their ability to select and optimize their NGS approach.”

Leveraging Novel Tools and Liquid Biopsy Expertise

One application of liquid biopsies is counting circulating tumor cells (CTCs) that are shed from solid tumors into the bloodstream and can develop into metastases. CTCs are powerful prognostic factors and potential biomarkers in cancer research. In addition to being easier to obtain, these cells are a useful surrogate for tissue biopsies and are likely to represent more invasive tumor subpopulations.

Novel technologies that capture and analyze the full spectrum of CTCs can help realize the full potential of these cells as biomarkers. One of these tools is microfluidics-based separation which separates CTCs from healthy cells based on physical differences. Other commonly used methods separate CTCs based on the interaction of antibodies with cell surface antigens. This can be confounding as heterogeneous subpopulations of tumor cells may show variance in surface antigens or even a loss of those markers needed for separation using antibody-based approaches. Microfluidics-based separation relies on inherent differences between normal and cancer cells, resulting in better sampling on the tumor and greater ability to detect cells that may have lost their epithelial markers during the epithelial-mesenchymal transition.

Precision for Medicine uses a proprietary technology, ApoStream®, which is unique in its approach to CTC isolation and enrichment. Using a diaphoresis-based, antibody-independent separation approach, ApoStream isolates and enriches CTCs and other rare or difficult-to-identify cells. An added benefit of ApoStream is that isolated cells remain intact for any type of downstream analysis, including multiplex immunofluorescence (mIF), next generation sequencing (NGS), fluorescence in situ hybridization (FISH) or ISH, in vitro assays, and even animal models. These downstream analyses can be performed at multiple timepoints to assess pharmacodynamics or perform additional cell characterization.

By bringing together comprehensive biospecimen solutions, deep scientific knowledge, technical laboratory expertise, and advanced data sciences, Precision for Medicine is built to push the boundaries of biomarker-driven research and development.

“Liquid biopsy technology has now advanced to a point where it is possible to analyze the genetic material at the single-cell level and even study spatial and temporal dynamics,” said Fannon. “With its myriad applications, from elucidating mechanism of action to predicting response to treatment, liquid biopsy will continue to increase in utility and this NGS initiative will enable our clients and the industry to move those applications forward.”

 

To learn more about the Precision Oncology Sequencing Initiative(Project P.O.S.I.) and Precision for Medicine, Biospecimen Solutions, visit www.PrecisionBiospecimens.com.

 

References
1. Ramalingam SS, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41-50.
2. Marabelle A, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol 2020;38(1):1-10.
3. Slamon DJ, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-792.
4. Cobain EF, et al. Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol. 2021;7(4):525-533.