Liquid Biopsy: the future gold standard?

Keerthi Ranganathan

Scientific Content Developer
4baseCare

Liquid biopsy is at the dawn of a new era of diagnosis and management of cancer. Before the evolution of liquid biopsy, tissue biopsies continued to dominate as the “gold standard” for diagnosis and treatment of cancer. However, tissue biopsy has various limitations in cancer diagnosis which are overcome by liquid biopsy. Hence, we can consider liquid biopsy as “the future gold standard” for the diagnosis and management of cancer.

Why liquid biopsy is future gold standard?

1. 1. Fluid phase less-invasive biopsy

Liquid biopsy is a minimally invasive or non-invasive technique, also known as fluid biopsy or fluid phase biopsy. It is done by taking bodily fluids like blood, urine, cerebrospinal fluids and stool samples from the patient for the diagnosis of cancer. However, tissue biopsy, which is the classical method for the detection of cancer, is invasive, painful and requires anesthesia, which caused discomfort in cancer patients. Sometimes a hospital stay and adverse events are also associated with tissue biopsy.

1. 2. Real time analysis of cancer

Liquid biopsy is capable of revealing the genetic features of individual tumors in real time and hence, it improves early detection, prognostication and monitoring treatment responses and information about developed resistance. Tissue biopsy sampling provides static and spatially limited information about the tumor at the time of the surgical procedure. However, cancer due to genetic heterogeneity continuously changes its state between the primary and metastatic sites.

1. 3. Degradation free preservation of sample

In liquid biopsy, a sample can be easily withdrawn and preserved for accurate diagnosis. There is no addition of any kind of chemical which reduces the sample efficiency for molecular analysis. While in the majority of tissue biopsies, a sample is preserved in formalin and paraffin for routine pathology, which can also reduce the sample utility for advanced molecular analysis.

1. 4. Promising biomarkers for diagnosis

Liquid biopsy analysis for the diagnosis and management of cancer has been based on analytes or biomarkers of biological fluids. The main biomarkers are cell free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, tumor-educated platelets (TEPs), cell free RNAs, proteins and metabolites. Due to short half-lives of most of them, can diagnose the real time condition of cancer patients. They are not only used as biomarkers for diagnostic tests but also for detection of emergence of resistance to treatment.

1. 5. Helpful in personalized medicine

Samples are more easily obtainable throughout the management of the cancer and analysis of sample is performed by liquid biopsy. It can be easily repeated because of its less invasive nature and helpful for monitoring patients’ responses to therapy during and after the treatment to shift it towards personalized medicines.

1. 6. Detection of drug resistance and relapse of cancer

Liquid biopsy provides information of changes in tumor at molecular level during and after treatment and hence, it could be a potential tracker for the identification of causes for the development of drug resistance and provide choice of treatment. It can also be used to monitor the progression of cancer and act as a monitoring method for cancer patients who have completed treatment but are at higher risk of relapse of disease.

1. 7. Easy procedure of sampling

The procedure of sampling in liquid biopsy can be easily done irrespective of location of tumor and patient’s condition. The condition of the patient and location of the tumor may hamper the sampling in tissue biopsy.

1. 8. Detection of Intra-tumor heterogeneity

Liquid biopsy is helpful in detection of intra-tumor heterogeneity by capturing tumor’s mutational status which cannot be possible with tissue biopsy.

1. 9. Detection of MRD and selection of choice of treatment

The detection of MRD through analytes of blood is imperative by using liquid biopsy, which could help in selection of treatment for MRD patients. Liquid biopsy along with NGS techniques provide highly sensitive detection of minimal residual disease (MRD) in cancer. With the help of liquid biopsy, evaluation of whether treatment escalation improves cancer outcomes in MRD-positive patients and treatment de-escalation is safe in MRD-negative patients is possible.

1. 10. Precision medicine

With the advancement of genomic sequencing techniques using NGS, detection and monitoring of therapy becomes much easier, more rapid and less expensive to access comprehensive genomic information of the tumors. There is a high possibility that usage of such genomic profiles contributes to the precision medicine of cancer patients.

1. 11. Early detection of cancer

The ability to detect cancer at earlier stages has the potential to reduce cancer mortality. Currently, tissue biopsy is the classic method for cancer diagnosis in solid tumors but its application is limited in early and non-symptomatic cancers detection. Liquid biopsies are largely utilized to gather information on tumors in order to detect early stage cancer and play a crucial role in the prevention and treatment of cancer.

In 2013, CELLSEARCH CTC kit approved by the FDA to monitor the cancer patients with advanced metastatic breast, colon and prostate cancers based on the CTCs concentration in plasma and other body fluids. In 2016, the FDA approved a liquid biopsy test, called the cobas EGFR Mutation Test for the detection of EGFR gene mutations in ctDNA of a patient’s plasma with lung cancer. Recently the FDA approved the first two NGS-based liquid biopsy solutions: Guardant360 in August, 2020 and Foundation One CDx in November 2020. More clinical tests have to be approved for better diagnosis of all types of cancer.

After gathering the advantageous potentials of liquid biopsy in diagnosis and management of cancer at any stage and find liquid biopsy to overcome all the major limitations of tissue biopsy, we can say that liquid biopsy is the future gold standard in the diagnosis and management of cancer. However, more standardized and established methods are the unmet need of use liquid biopsy in clinical practice.

Reference

1. Poulet G et al. 2019. Liquid Biopsy: General Concepts. Acta Cytol. 63(6):449-455.

2. Honore N et al. 2021. Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact. Cancers; 13(21): 5364.

3. De Rubis G et al. 2019. Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis.  Trends Pharmacol Sci. 40(3):172-186.

4. Chen M and Zhao H. 2019. Next-generation sequencing in liquid biopsy: cancer screening and early detection. Hum Genomics. 13(1):34.

5. Andersson D et al.2020. A Liquid biopsy analysis in cancer diagnostics. Mol Aspects Med. 72:100839.

6. Dominguez-Vigil IG et al. 2017. The dawn of the liquid biopsy in the fight against cancer. Oncotarget. 9(2):2912-2922.