Over the last decades, the concept of precision medicine has dramatically renewed the field of medical oncology; the introduction of patient-tailored therapies has significantly improved all measurable outcomes. Liquid biopsy is a revolutionary technique that is opening previously unexpected perspectives. This approach is being pioneered by several companies and is expected to bring multiple benefits, not least the fact that such tests are relatively quick and easy to perform and are far less invasive than tissue biopsy.It consists of the detection and isolation of circulating tumor cells, circulating tumor DNA and exosomes, as a source of genomic and proteomic information in patients with cancer.
Primary tumor and metastatic sites are also able to esfoliate vital cells that, once entered into the bloodstream, are circulating tumor cells (CTCs). Many technical hurdles have been resolved thanks to newly developed techniques and next-generation sequencing analyses, allowing a broad application of liquid biopsy in a wide range of settings. Initially correlated to prognosis, liquid biopsy data are now being studied for cancer diagnosis, hopefully including screenings, and most importantly for the prediction of response or resistance to given treatments. In particular, the identification of specific mutations in target genes can aid in therapeutic decisions, both in the appropriateness of treatment and in the advanced identification of secondary resistance, aiming to early diagnose disease progression. Still application is far from reality but ongoing research is leading the way to a new era in oncology.
Advances in technologies, particularly the introduction of NGS techniques, are contributing to increases in the appropriateness of liquid biopsy. However, large-scale and multicenter trials are also ongoing to confirm all the potentialities that are now being studied in order to fully define the exact settings and conditions for the application of liquid biopsy and confirm the comparison of performance with current solid biopsy methods. liquid biopsy allows researchers to identify cancer cells in the blood that die from natural causes or treatment. In past studies conducted with multiple cancers, it has been observed that the cancer cells in a tumor release fragments of DNA into the bloodstream. This freely circulating tumor DNA found in the blood is called ctDNA and can be detected in liquid biopsy samples.
Although the main target of efforts to develop liquid biopsy products up to now has been cancer, the technology also has other potential applications, such as prenatal diagnosis of chromosome abnormalities via a blood sample or monitoring chronic kidney disease via urinary proteome analysis. It’s very crucial for early detection of mutant genes to identify cancer and its subtypes, for effective management strategy of the disease. Advances in genomic-analysis technology have made it possible to analyse vanishingly small amounts of DNA in biological samples. Many clinicians now use liquid-biopsy tests that can profile mutations and other abnormalities in circulating tumour DNA.
Relatively little is known about the provenance of this DNA, but it is thought to be released by dying cancer cells and seems to be remarkably representative of tumour genomic diversity.In the past decades, numerous studies have shown the potential clinical utility of liquid biopsy, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and circulating tumor exosomes for various cancers, including cancer
Circulating cell-free DNA derived from tumors is likely to represent the entire genomic landscape of the tumor and can serve as a liquid biopsy to analyze tumor-specific genetic and epigenetic alterations. In a seminal study, it was discovered that cancer patients had much higher levels of cell-free DNA in their blood compared to healthy individuals. The ability to study genomic profile of cancer cells through noninvasive sampling of blood or other body fluids represents one of the most exciting and rapidly improving fields in cancer. Liquid biopsy describes a broad range of screening techniques used on samples that can be collected in a relatively non-invasive way, rather than directly from the tumour. The biopsies often involve blood, but not always — some researchers are exploring the possibility of testing urine, stool and saliva samples, which might offer better windows onto malignancies in some tissues.
Recently, liquid biopsy has largely demonstrated to be a surrogate of tumor tissue for noninvasive assessment of tumor-linked genetic and epigenetic alterations and has recently entered into clinical use for predicting response and monitor resistance to targeted therapies in the setting of advanced disease. Because of its several clinical advantages compared to tissue biopsy and, thanks to development of newer, sensitive technologies to analyse a larger number of biomarkers, liquid biopsy has been suggested for a wide range of clinical applications, including early diagnosis of cancer as a potentially curable disease. There are several distinct indicators of cancer that researchers can look for in liquid biopsies. The earliest efforts focused on the detection and analysis of circulating tumour cells (CTCs). These are either detached components of the main tumour or indicators of ongoing metastatic spread, and therefore valuable signals of aggressive disease. CTCs are typically scarce — even with aggressive disease, they might be present at levels lower than a single cell per millilitre of blood. Furthermore, some tumours are more likely to shed cells into circulation than others.