Use of liquid biopsy analysis to identify biomarkers related to solid tumors: Insights from a recent Japan symposium (Part 2)
Liquid biopsy analysis offers a promising, minimally invasive approach to detecting and monitoring cancer. It involves the analysis of tumor components like DNA, cells and exosomes found in body fluids. Unlike traditional tissue biopsies, liquid biopsies allow for repeated sampling to track tumor evolution and response to therapy in real time. In his presentation at the recent Japan Symposium 2023, Dr. Sriram Ramanan, associate director of oncology biomarkers at Labcorp’s Biomarker Solution Center, discusses the advantages and disadvantages of using liquid biopsy analysis to identify biomarkers related to solid tumors.
In liquid biopsies, the two main components analyzed are circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA). CTCs were first observed in 1869, but their clinical use has been limited by their rarity and the technical challenges of isolating them from blood. In contrast, ctDNA analysis has become more feasible with advances in sequencing technology. ctDNA allows detection of mutations, copy number variations and other genomic signatures associated with cancer. However, ctDNA only comprises 0.1%-10% of total cell-free DNA.
Applications in cancer care
Liquid biopsies show promise for noninvasive genotyping to guide targeted therapy selection, monitoring response to treatment, detecting resistance mechanisms and tracking minimal residual disease (MRD) after therapy.
Early cancer detection is crucial to improving survival rate and reducing treatment costs for patients. Liquid biopsy has shown promise in enabling screening and saving lives through early intervention. Liquid biopsy tests have also received FDA approval for screening asymptomatic individuals for early detection of cancers like colorectal cancer. Tests like Epi proColon® and CancerSEEK analyze blood for methylated DNA or protein biomarkers to detect colorectal, ovarian and other cancers at early stages.
In late phase trials, liquid biopsy enables noninvasive monitoring of response and MRD (the small number of cancer cells that remain in the body during or after treatment). For example, studies have shown ctDNA can detect tumor relapse months earlier than imaging in breast cancer patients. Assessing MRD helps classify relapse risk and inform decisions about treatment escalation or de-escalation.
Limitations of liquid biopsies
Notably, liquid biopsies cannot fully replace tissue biopsies, which remain the gold standard for cancer diagnosis and characterization. Liquid biopsies have higher false negative rates because of factors like low levels of tumor material in the blood. They are also prone to false positives from contamination and errors. Tumor heterogeneity can also lead to under-sampling of the diversity of genomic clones. Additionally, standardized protocols are still needed to implement liquid biopsies effectively across settings. While liquid biopsies have limitations, research continues to improve their accuracy and expand their clinical utility. Efforts are underway to validate them as complements to tissue biopsy.
Labcorp’s liquid biopsy offerings
Labcorp offers a range of liquid biopsy solutions utilizing both next-generation sequencing (NGS) and platforms for polymerase chain reaction (PCR). For example, PGDx elio™ plasma complete uses NGS to analyze over 500 genes from plasma for biomarker discovery across solid tumors. PGDx elio plasma resolve and Labcorp Plasma Focus™ test known biomarkers for therapy selection and monitoring. On the PCR side, Labcorp utilizes the cobas® EGFR Mutation Test v2 to detect EGFR mutations in 42 genes and cMET exon 14 skipping.
Liquid biopsy analysis has many applications across the clinical trial continuum. In early phase trials, it facilitates comprehensive genomic profiling for patient selection. Liquid biopsy can also identify mechanisms of resistance to guide therapy switching. For instance, in the AURA3 trial for non-small cell lung cancer, liquid biopsy detected the emergence of new mutations like KRAS and MAP2K1 at progression on EGFR inhibitor therapy.
The Labcorp Biomarker Solution Center
The Labcorp Biomarker Solution Center provides scientific support and consultation for the development of biomarker strategies to aid in clinical trial success. Since 2018, the center has participated in over 2,000 oncology trials across various solid tumors and blood cancers. The center has provided guidance on biomarker strategies, companion diagnostic development and patient stratification requirements for over 900 requests. Labcorp offers scientific expertise based on experience with hundreds of clinical programs to help navigate biomarker testing through our extensive network of laboratories. The center provides consultation on sample acquisition strategies, can develop companion diagnostics in parallel to speed up drug commercialization and offer therapeutic area focus to obtain the most relevant information from trials to support successful commercialization. Beyond oncology, the Biomarker Solution Center has experts in other areas like neurology, immunology, diabetes and metabolic disorders.
With options for biomarker discovery, therapy selection, monitoring and early detection, liquid biopsy is transforming how we understand, diagnose and treat cancer. Labcorp’s liquid biopsy offerings, backed by the extensive capabilities of the Biomarker Solution Center, add significant value to clinical programs, as well as research, discovery and drug development programs. This can generate evidence to support regulatory approvals for companion diagnostics and make personalized medicine a reality for patients.