July 29, 2020

Liquid biopsy in cancer diagnosis and treatment

By Donald Green, Field Application Scientist USCAN, Genomics and Diagnostics

Liquid biopsy, a non-invasive alternative to tissue biopsy, is changing cancer diagnosis, treatment and even screening. Advances in genomics make it possible.

Imaging may show tumor size changes and metastases, but it will not reveal changes at the molecular level. Tissue biopsy is highly invasive, not to mention resource intensive and costly. Liquid biopsy, by comparison, is minimally invasive, yet provides detailed information about tumor cells and indicates possible therapeutic pathways.

Liquid biopsy reveals new levels of specificity

The blood from a cancer patient contains detectable levels of genetic material from a tumor in the form of circulating tumor DNA (ctDNA), a type of non-encapsulated (cell-free) DNA that originates in the tumor and can be found in the blood stream. There is a wealth of information contained within the ctDNA, including known genetic mutations that can help predict the clinical response and guide both conventional and novel treatments.

Liquid biopsy can reveal not only tumor markers that indicate sub-types of cancer (interpatient heterogeneity), but also markers for subpopulations of cells within a tumor (intratumor heterogeneity). If these markers change over time as the tumor responds to treatment, liquid biopsy can reveal those changes.

Interpatient heterogeneity: variations from patient to patient

Next-generation sequencing (NGS) with liquid biopsy can detect specific genetic tumor markers, which vary from patient to patient. A specific mutation can indicate that the tumor would be more receptive to one therapy or resistant to another. Therefore, identification of the biomarkers that are specific to a patient’s tumor can guide the clinician to the most efficacious treatment.

Intratumoral heterogeneity: understanding cell subpopulations within tumors

Recent research has shown that there are subpopulations of cancer cells with distinct genomes in different regions of tumor. The different genotypes can be detected with tissue biopsy, but that is hit or miss, depending on which part of the tumor is excised. Liquid biopsy can be more accurate in detecting tumor cell subpopulations. NGS technology has enabled the identification of rare subpopulations only present in a small fraction of the overall tumor mass.

Monitoring cancer treatment efficacy and resistance

The more information that is available to a clinician, the better they can monitor and understand the progression of the disease. Liquid biopsy can be used to monitor disease progression and investigate treatment resistance.

For example, non-small cell lung cancer (NSCLC) patient who initially tested negative for a resistance mutation can later acquire resistance. This would indicate to the clinician that the patient has progressed and should consider moving them onto another therapy.

Resistance can also develop when solid tumors recur at the primary site after treatment or metastasize to distant sites. Due to intratumor heterogeneity and selective pressure throughout tumor treatment, the biomarkers that were initially detected might no longer represent the current disease. In this case, the initial therapy may be ineffective. Liquid biopsy can reveal this and guide a change to a more effective therapy.

Liquid biopsy: an oncology game-changer

Liquid biopsy can be sampled from a diverse range of fluids including blood, urine, cerebrospinal fluid, saliva, stool, and lavage fluids. Due to ease of sample collection, liquid biopsy opens up alternative approaches for cancer diagnosis and patient care. Liquid biopsy tests can be repeated as often as is necessary to monitor a patients’ progress during therapy. Liquid biopsy might allow earlier detection of disease progression, revealing changes even before they are observable by conventional imaging approaches or by blood protein marker changes in the patient.

Due to the appreciably lower cost, invasiveness and time required to perform liquid biopsy, the approach supports the screening of at-risk population groups by simple routine testing. This substantially increases the possibility for the early detection of many cancers and, as a result, could increase overall patient survival through timely initiation of treatment and surgery. We can already see liquid biopsy used for routine screening with Cologuard™, an approved liquid biopsy (stool) test for colorectal cancer screening.

The potential impact of liquid biopsy in oncology is only just starting to be realized. NGS provides an opportunity to increase the capabilities of liquid biopsy diagnostics by identifying additional relevant mutations. As we discover more genetic markers and develop more therapies to target these markers, we can also expect to see increased availability and use of liquid biopsies to aid in cancer diagnosis and treatment.

Read our whitepaper, Investigating cell-free DNA in liquid biopsy, for a deeper look into the challenges in measuring ctDNA or cfDNA in liquid samples, the enabling genomics technologies, and the clinical opportunities for liquid biopsy.