A tissue biopsy can be painful, and recovery difficult. But now, thanks to advances in genomics research, only a blood sample is needed in some cases. See the difference molecular diagnostics is making to patients.
“It’s cancer…”
Those words are scary to any patient. They often come after diagnosis has been confirmed by testing. In lung cancer, this usually involves biopsy. A traditional biopsy involves extracting a piece of tissue for diagnostic tests. Although tissue biopsies are routine, they aren’t without risk.
A lung tissue biopsy is a delicate and potentially life-threatening operation. Potential complications, which require considerable post-op care and a long recovery period, can include a punctured lung, coughing up blood, chest pain, shortness of breath—even panic attacks. But the biopsy is necessary, not only to confirm the cancer diagnosis, but also to determine the type of cancer. We will use non-small cell lung carcinoma (NSCLC) as an example.
There are various treatment options for NSCLC, dependent on knowing a bit more about the patient’s specific cancer. Often, a second biopsy is necessary to identify the most appropriate treatment option. Fortunately for some patients, the second biopsy may use a new technique requiring only a blood sample: a liquid biopsy.
What is a liquid biopsy?
Liquid biopsies are a non-invasive alternative to traditional tissue biopsies. A blood sample can contain a detectable level of genetic material from a tumor in the form of circulating tumor DNA (ctDNA) that provides the material needed for a molecular diagnostic test. The ctDNA is sequenced to identify known genetic mutations in the tumor DNA.
How does the liquid biopsy for NSCLC work?
There are many liquid biopsies with associated molecular diagnostics that are still in the research and development phase, but there is an approved test in the US for patients with NSCLC.
A specific mutation can indicate that the tumor would be more receptive to one therapy or resistant to another. This is the case with the FDA-approved cobas™ EGFR Mutation Test v2 which identifies whether patients have mutations in the EGFR gene. This vital information helps oncologists determine the most suitable treatment option for a given patient.
This specific liquid biopsy can also be used to monitor disease progression and check for treatment resistance. For example, a NSCLC patient who initially tested negative for a resistance mutation can later acquire it. This would indicate to the clinician that they should move the patient onto another therapy.
A drop of blood. A diagnostic test.
For the cancer patient, the liquid biopsy is a relatively painless process. It is actually reassuring for many patients to learn that they can then be treated with a drug specifically designed to target their own cancer. They can also expect further liquid biopsies to monitor their cancer for changes, enabling their oncologist to adjust the treatment as needed.
The ability to provide targeted treatment based on a deep understanding of the cancer at the molecular level gives patients and their families new hope. For many, in addition to improving outcomes, this can also have a profound emotional impact. With a more positive outlook, patients can plan for the longer term and look forward to sharing important milestones and events.
DNA sequencing and the next generation of diagnostic tests
For now, the only approved test for liquid biopsies relies on using real-time polymerase chain reaction (PCR), a technique for amplifying, or multiplying, minute quantities of genetic material, such as ctDNA. This material can then be sequenced to identify a limited range of known mutations. Next-generation sequencing (NGS) provides an opportunity to increase the capabilities of liquid biopsy diagnostics by identifying additional relevant mutations.
Indeed, techniques for DNA amplification combined with NGS make it possible to generate quality data by sequencing the genetic material derived from a single cell or even DNA fragments, such as ctDNA, which are circulating in the blood. Right now, there are a multitude of NGS-based NSCLC tests in development for liquid biopsies.
For example, the LungSelectTM test aims to screen for a whole panel of genetic alterations, beyond those of the common mutations in EGFR. The idea is that NGS will enable mutation identification with a very high degree of specificity and sensitivity.
All this is welcome news to patients.
As we discover more genetic markers and develop more therapies to target these markers, DNA amplification and NGS techniques will enable liquid biopsies and associated tests that aid in the diagnosis and treatment of other cancers. Similar testing using fetal DNA fragments which are present in the mother’s blood are already widely used for pre-natal testing.
Patients look forward to a day when hearing, “It’s cancer,” no longer means they need to face potential complications from a traumatic traditional tissue biopsy or worry about further invasive biopsies during the long battle to get well.
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