Profiling an active cancer and assessing response to a therapy have traditionally relied on invasive surgeries to obtain biopsy samples. This approach has several limitations, the most prominent of which is invasiveness. In addition, collecting multiple biopsy samples to accurately measure treatment response is not feasible. Tumours are highly heterogenous, rendering the biopsy site a limited “snapshot” which does not represent the holistic view of the tumour mass. Multiple biopsies may therefore be required in such cases and particularly where there is metastasis.
Oncology research is adopting an approach which analyses various biological fluids as “liquid biopsies”. Blood derivatives like serum and plasma are the most common of these, however, liquid biopsies can also include mucosa, pleural effusions, urine, saliva and cerebrospinal fluid (CSF). Analytes in liquid biopsies can include circulating tumour cells, circulating tumour DNA, tumor-derived extracellular vesicles (EVs), micro RNA’s and tumour-educated platelets.
Figure 1. Analytes from liquid biopsies and their application. Ref: Lone et al. Mol Cancer 21, 79 (2022).
There are a variety of methods for analyte detection including ELISpot to characterise tumor secretory proteins and mutational profiling. Circulating tumour DNA can be analysed using a targeted approach for specific gene arrangements/mutations or broader analysis of the tumour genome. However, methods for sample handling, isolation and analysis of circulating tumour DNA have yet to be fully standardized. EVs carry cargo originating from the tumour cells they are released by and allow tumour cells to communicate and evade treatment. EV cargo can therefore include cancer-specific biomarkers. Translational studies have further indicated that tumour-derived EVs can influence non-malignant organs and tissues and are therefore critical components of disease pathology.
There are some important limitations of liquid biopsies worth noting. It is not yet considered as standard practice, therefore it is currently used as complementary to existing biopsy sampling. In some cases, biomarkers are considered “fragile” and are therefore transient and not robust enough to reliably inform clinical decisions. The sample types limit the use of enrichment techniques and in such cases, limited assay sensitivity reduces utility. Despite some of these limitations, technology platforms continue to improve and liquid biopsy sampling is becoming more and more widely applied.
Some use cases include:
- Metabolomic profiling in liquid biopsy samples which informed cancer biomarker discovery.
- Tumor-tissue-modified viral HPV-DNA demonstrated 100% specificity in diagnosis and surveillance of HPV-associated oropharyngeal cancer.
- In patients with non-small cell lung cancer, brain metastasis can occur in up to 45% of patients with advanced disease. A proof-of-concept study demonstrated how circulating tumour DNA and EV RNA analysis in CSF represented a potential surrogate for brain metastasis biopsies. In addition, the CSF-specific biomarkers could then serve as potential drug targets.
At Synexa, we have over 20 years of experience in the field of biomarker analysis. Combining the latest technology and access to patient samples have allowed us to provide valuable insights for our clients in numerous clinical and translational studies. We have a range of platforms which can permit multiplexed soluble biomarker analysis with as little as 1 μl of sample and in some cases, quantification in the femtogram range. Our flow cytometry and ELISpot platforms give us deeper insights into cellular biomarkers while our digital PCR and sequencing platforms can be applied to circulating tumor DNA analysis. If you would like to find out more, please email us at [email protected].
Written by Dr. Nicholas Woudberg (PhD)
References:
- Ferrandino et al. JAMA Otolaryngol Head Neck Surg (2023).
- Lone et al. Mol Cancer 21, 79 (2022).
- Tsakonas et al. Lung Cancer. Jul 3;182:107292 (2023).
- Wang et al. Biomark Res. Jun 30;11(1):66 (2023).
