Biomarkers & Liquid Biopsies in Cancer
What is a Biomarker?
The National Cancer Institute defines a biomarker as “a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.” Biomarkers may be produced by both normal cells and cancer cells, but are often up-regulated or misregulated in cancer.
What Are the Different Types of Biomarkers?
Types of biomarkers include: genomic (DNA, RNA, miRNA), proteomic (proteins or autoantibodies) or metabolomic (lipids, metabolites). The later of these are indicative of current patient state versus “potential downstream effects.”
Various Blood-Based “Liquid Biopsy” Approaches Include:
- Circulating Tumor Cells (CTCs)—Tests based on CTC capture can detect tumor cells in the blood that have been shed by the primary tumor. CTCs are extremely rare in the circulation, approximately one CTC per billion circulating cells, making the approach of this technologically difficult. Furthermore, additional discovery work will be required to determine the origin of isolated CTCs (i.e. what is the primary tumor type?). Therefore, before CTCs can play a role in the routine detection of cancer, significant analytical development and clinical validation will be required prior to commercial adoption.
- Circulating Nucleic Acids (e.g. ctDNA, ctRNA and microRNA (miRNA))—Tests based on circulating nucleic acids involve isolating remnants of tumor cells within the blood stream. Previous studies have found that ctDNA can be detected in the blood in approximately 50 to 90 percent of patients, depending upon cancer type.5 The study also found that ctDNA could be used to identify clinically relevant gene mutations, which could help oncologists select an appropriate treatment regimen.5 The challenge with this approach is the limitations of finding abnormalities within DNA that are the targets of a specific search. ctDNA is found using primers specific for a given gene or genes. At present it is not practical to cast a wide net for just “mutated” ctDNA sequences in asymptomatic patients. The test will pick up normal DNA along with mutations which raises the question “is it a real mutation or just an artifact.” As discussed above, significant discovery work, analytical development and clinical validation will be required to determining the origin of ctDNAs prior to commercial adoption.
- Proteomics (protein biomarker-based liquid biopsies)—Tests based on proteomics detect cellular proteins, which may be secreted and/or misregulated in response to disease. Proteins are the mediators of cellular growth (including tumors) and proteins are encoded by genes. However, gene mutations/changes do not necessarily lead to the creation of a mutated protein and may or may not impact tumor growth. Healthy cells have processes to correct most DNA abnormalities before mutant proteins can be made. In cases where tumor cells have misregulated proteomics, the protein biomarkers can often be detected in bodily fluids (such as blood, serum, urine, etc.) more readily than CTCs or ctDNA.
Learn more about the roles of biomarkers in breast cancer and different liquid biopsy approaches in this free guide: Unlocking the Power of Proteins