Liquid Biopsy: From an Improbable Idea, New Potential Emerges

By Prasanth Reddy, MD, MPh, FACP, VP, Medical Affairs, Foundation Medicine and Lucas Dennis, Senior Director, Franchise Development, Foundation Medicine

It’s always been an ambitious concept: By analyzing a patient’s blood, doctors might better understand their individual cancer, and thus better pinpoint what treatment options may be most effective. But yesterday’s ambition has become today’s reality—we’re living in an exciting time for this kind of test, known as liquid biopsy.

For years, Foundation Medicine has been using traditional tissue biopsies to uncover deep insight into the genomic drivers of cancer. But, as the science of liquid biopsies continues to advance, a patient’s blood can provide a snapshot of what’s going on inside a tumor without having to go inside the tumor.

This innovative process was made possible through the discovery and understanding of how tumors shed cancer DNA into the blood stream in the form of cell free DNA. On top of that, the technology that can analyze this DNA has rapidly evolved in recent years, bringing levels of sensitivity that were previously unachievable.

Now, as new potential emerges for liquid biopsy, it’s worth taking a look back to appreciate the scientific rigor, dedication and passion that has helped overcome seemingly insurmountable challenges on the path toward bringing this technology to everyday care for advanced cancer patients.

Foundation Medicine’s liquid biopsy test, FoundationOne Liquid, uses a standard blood draw to analyze tiny amounts of circulating tumor DNA (ctDNA). These fragments of cancer DNA can shed from a tumor into the bloodstream and may contain important genomic insights that can help inform physician’s treatment decisions around options including targeted therapy, immunotherapy or clinical trials.

Liquid Biopsy: An Important Option for Patients

For years, tissue biopsies have been the standard for genomic testing. Unfortunately, not all patients are able to get a tissue biopsy that would allow providers to access genomic information about their tumor. This can happen for many reasons: the tumor itself is inaccessible via the surgery required to get a tissue sample, there isn’t enough tumor tissue available, or the patient is too sick for a tissue biopsy procedure. Research has shown that 30 percent of patients with non-small cell lung cancer (NSCLC) do not have adequate tissue available at diagnosis for standard biomarker testing. [1]

The bottom line is, liquid biopsies allow more patients to access the genomic information within their cancer at a level that, according to several studies, it equal to traditional tissue testing. In fact, recent research showed that Foundation Medicine’s liquid biopsy test identified patients with ALK fusions who are likely to respond to alectinib (Alecensa) at a frequency consistent with historically published data from tissue testing.[2]

There’s no doubt we’ve reached an incredibly exciting time for liquid biopsy, seeing first-hand the value it brings in the clinical setting. But it’s also important to note that reaching this milestone has required decades of research and advancements in science.

An Important Journey

The first steps toward liquid biopsy came with the discovery of cell free and free RNA circulating in human blood in 1948.[3] ctDNA has been used for years to monitor patients after they receive treatment for advanced cancer. ctDNA reflects all the places that tumors from a cancer might spread in the body, and can pick up any potential genomic differences from cancer cells in these locations.[4] This early work to understand tumor biology and how to detect DNA from tumor fragments that circulate in the blood, combined with major advancements in the power of these tests – liquid biopsy tests need to be 10-times more sensitive than tissue tests to detect the small quantities of genetic material in the blood – paved the way for liquid biopsy as we know it today.

In 2016, the FDA approved the first liquid biopsy test to detect a single genetic mutation in a non-small cell lung cancer tumor.[5] Now liquid biopsy tests like our FoundationOne Liquid assay can analyze several cancer genes at once. We’ve accomplished this dual goal of high sensitivity and broad analysis through a unique blend of strategies: dozens of underlying software subsystems and complex algorithms, deep expertise in cancer genomics and carefully optimized lab workflows.

Packing all of this analytical power into analyzing a standard blood draw is no small task. Hundreds of people spent years building Foundation Medicine’s liquid biopsy assay ensuring it met the highest level of quality standards. Seeing all that work lead up to the test’s use in initial trials, and then finally confirming it could match patients to targeted therapies, is something our team of collaborators will never forget.

Looking Ahead for Liquid Biopsy

Additional validation for comprehensive liquid biopsy tests may be on the horizon. A version of our FoundationOne Liquid test, analyzes more than 300 genes, plus MSI and blood tumor mutational burden (bTMB), both important genomic signatures that can help predict whether a patient might respond to immunotherapy.

As liquid biopsy tests continue to expand access to comprehensive testing for more patients across multiple types of cancer, we’ll continue to enrich our deep understanding of cancer and how it grows. This, in turn, fuels the development of new targeted therapies, making precision medicine accessible to more patients.

And that, at the end of the day, is what’s most inspiring: We’re enabling physicians to make informed treatment decisions for their patients regardless of their condition, while simultaneously pushing the science forward every day. Liquid biopsy has come a long way toward providing a high-quality, minimally invasive testing option to deliver important genomic insights for advanced cancer patients. That’s why, as we aim to advance access to precision medicine, we’re fueled by optimism and excitement for a better tomorrow.