One of the first tests a physician conducts on a patient with a suspicious lump on his or her body is a tissue biopsy. Analysis of tissue biopsies is crucial in both the diagnosis and characterization of most cancers; however, they have limitations. For one, tissue biopsies can be painful, costly, risky and invasive. These difficulties may make obtaining multiple biopsies on a patient impractical. More importantly, tumors change over time as they grow and metastasize . Therefore, a tissue biopsy at one part of the body may not adequately represent cancer at another location in the body. Additionally, a biopsy taken when the cancer was first diagnosed may not reflect the cancer at a later point in time .
In light of these limitations of tissue biopsies, scientists have been exploring a new approach that is less invasive and better equipped to capture the dynamic nature of tumors. This new approach, called liquid biopsy, relies on analyzing tumor material—fragments of DNA as well as cancerous cells—that are found in bodily fluids, usually blood . Tumor material from all sites of disease is released into circulation allowing scientists to capture its heterogeneity and a more representative view of the cancer throughout the body. Tumor material, such as DNA, can then be assessed for genetic and epigenetic aberrations, providing a genetic landscape of the cancerous lesions in a patient and the opportunity to track how this genetic landscape evolves over time .
One of the implications of this is liquid biopsies may aid in precision cancer treatment since they can identify molecular characteristics of an individual’s cancer. In fact, liquid biopsies are currently being used to guide clinical decision making and determine optimal treatment. In 2016, the FDA approved the first liquid biopsy test, which analyzes circulating tumor DNA and allows for the detection of mutations in the EGFR gene in patients with non-small cell lung cancer (NSCLC), the most common type of lung cancer . The purpose of this test is to identify patients that may be eligible for targeted therapies that kill cancer cells with EGFR mutations . While this liquid biopsy test only focuses on one gene, current research is expanding to develop liquid biopsies that can analyze hundreds of genes.
Since they are easily repeatable, liquid biopsies may also be useful to monitor patients’ responses to a therapy, both during and after treatment is completed. In a meta-analysis looking at 50 studies with a total of 6712 patients with breast cancer, it was found that overall circulating tumor cells (CTCs) were significantly decreased after treatment . Additionally, the study showed that a reduction in CTCs was significantly associated with a decreased probability of disease progression and a longer overall survival period . The results of this study have shown that CTC status, which can be determined using a liquid biopsy, can be an effective indicator to monitor the efficacy of a treatment and predict patient outcomes.
Another application of liquid biopsies is for the early detection of cancer, when treatment has the highest chance of success. The logic behind this is that these biopsies may detect the presence of tumor material at an early stage when the tumor escapes detection by imaging methods. In fact, one study has demonstrated that CTCs can be identified in patients at risk of developing lung cancer one to four years before detection of a lung nodule by imaging . In these patients, lung cancer was diagnosed at an early stage allowing for immediate tumor resection, or surgical removal of the tumor . These patients had no tumor recurrence 16 months after surgery . Similar to early cancer detection, liquid biopsies can also detect post-treatment cancer that persists and cannot be found with medical imaging, a condition known as minimal residual disease . Analysis of tumor material from liquid biopsies can enable the detection of cancer recurrence months earlier than is possible with current imaging technologies . This is a significant development as many cancer patients experience recurrence years after a tumor resection.
Despite providing a broad range of applications in the field of oncology, scientists must overcome many obstacles before liquid biopsies can be widely integrated into the clinic. One major concern is the lack of technique standardization. Currently, there is no consensus in the extraction of circulating tumor DNA, storage of the sample and quantification of the sample . Variation within these procedures can cause the results of a single liquid biopsy to differ considerably and lead to problems in clinical interpretation. Regarding the use of liquid biopsies for early cancer detection, there are concerns about false positive test results and preemptive concern for potentially benign cancers . Only once these hurdles are overcome can liquid biopsies revolutionize cancer care. Nevertheless, they are a major breakthrough in the field of oncology and have the potential to transform screening, diagnosis, treatment and prognosis in patients with cancer.
Edited by: Alicia Yang