Liquid biopsies are one of the most promising new technologies for cancer care. In the recent past, the assessment of circulating blood markers as surrogate real-time biopsies of disease status has been extensively studied. Profiling of circulating tumor DNA (ctDNA), the tumor-derived fraction of circulating cell-free DNA (cfDNA), can be used to track disease development and progression in a non-invasive way. Numerous studies have shown its applications in various cancer types including lung, colorectal, prostate, liver, melanoma, breast, and pancreatic cancer.
In a recent Strategy of the Month article published in Trends in Molecular Medicine, Roy et al. depicted the role of ctDNA for cancer management. The evolution of technology has broadened the scope of its applications and studies on cfDNA have opened up new pathways in cancer diagnosis, and interventional clinical studies with defined outcome measures are now proving the clinical usefulness of ctDNA. Comprehensive cell-free DNA (cfDNA) analysis has consistently shown viability as an alternative to tissue genotyping, especially in tissue-limited or time-limited clinical scenarios. In this infographic, Roy et al. showed an overall picture of the clinical utility of cfDNA profiling for cancer management.
The Strategy of the Month also highlighted detection of ctDNA during routine cancer surveillance after treatment of early-stage disease and prior to imaging-detected disease. Its detection would indicate early growth of tumor cells after curative-intent therapy and could be used for earlier administration of systemic therapy in the setting of a clinical trial.
In addition, the illustration shows the clinical utility of ctDNA relapse, which is a specific term used to indicate detection of ctDNA during routine cancer surveillance after treatment of early-stage disease and prior to imaging-detected disease. Its detection would indicate early growth of tumor cells after curative-intent therapy and could be used for earlier administration of systemic therapy in the setting of a clinical trial. Imaging-detected relapse by CT scan may not occur until a tumor contains tens-to-hundreds of millions of cells (>0.5 cm) multiple months after ctDNA relapse is detected. This introduces the question of whether earlier administration of systemic therapy following ctDNA relapse detection would improve outcome instead of starting therapy after imaging-detected relapse when more cancer cells have grown.
Although there are some limitations for the optimum integration of such assays into clinical care, the U.S. Food and Drug Administration (FDA) has already approved several ctDNA-based liquid biopsy tests for companion diagnostics (CDx).[Note] In addition, various blood-based multi-omics studies utilizing artificial intelligence/machine learning (AI/ML) showed the clinical utility of ctDNA-based liquid biopsy, including Roy et al. during the AASLD 2020, where a multi-analyte ctDNA-based technology was utilized for early detection of hepatocellular carcinoma (HCC), which is one of the most prevalent liver cancers.
In the field of liquid biopsy, Dr. Roy has continually developed and integrated strategies across advanced diagnostic modalities, which offer diagnostic multi-omics profiling to the monitoring of radicality in surgical outcomes, from evaluating either response or resistance to systemic treatments to quantifying minimal residual disease with high specificity, allowing the collection of robust and reproducible data in a simple and non-invasive way using a blood sample. The current blood-based technology has been implemented for the detection of various cancer types. It is clear that liquid biopsy through the analysis of ctDNA will progressively be routinely used in the care of patients with cancer as it paves the way for a straightforward and personalized screening tool to see if a patient will respond to therapy or not.
In early August 2020, the U.S. Food and Drug Administration approved the first liquid biopsy companion diagnostic that also uses next-generation sequencing (NGS) technology to identify patients with specific types of mutations of the epidermal growth factor receptor (EGFR) gene in a deadly form of metastatic non-small cell lung cancer (NSCLC). This approval was the first to combine two technologies — NGS and liquid biopsy — in one diagnostic test in order to guide treatment decisions.
 Roy D, Lucci A, Ignatiadis M, Jeffrey SS. Cell-free circulating tumor DNA profiling in cancer management. Trends Mol Med. 2021 Jul 23:S1471-4914(21)00182-9. doi: 10.1016/j.molmed.2021.07.001. Epub ahead of print. PMID: 34312074.[Article]
Illustration used with permission from the Authors of the article published in Trends in Molecular Medicine, © 2021 Elsevier.
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