Dr Suruchi Aggarwal, Ph.D. (Human Genomics), Lead, Scientific Affairs & Technical Support – Oncology, MedGenome explains why liquid biopsy is a breakthrough in cancer treatment
Cancer is the second leading cause of death globally. In India, the number of cancer cases reported annually is set to rise from 14.6 lakh in 2022 to 17.3 lakh in 2025. Unfortunately, a whopping 75 to 80 per cent of those diagnosed are estimated to have advanced-stage tumours, making treatment challenging and the outcomes less favourable.
With cancer, timing is everything. According to a recent news report, Detecting cancer at Stage 1, translates to an 85 per cent chance of a cure while with stage 3 cancer, that drops to about 30 per cent. The rising incidence of cancer has made preventive diagnostics and accurate screening for cancer the need of the hour.
The role of genetic testing in changing the cancer story
So, what can we do to change course? The United States has succeeded in reducing the cancer death rate by 33 per cent since 1991, in part through a combination of new treatments and screening. Genetic testing is an excellent new tool in the arsenal that is now available in India. We are now one step closer to early diagnosis and screening, prediction of prognosis (how the disease will progress) and precision medicine (targeted treatment options), improving outcomes for patients.
With the availability of cost-effective genomic testing in India using free-flowing DNA released in the blood from growing tumor tissue (liquid biopsy), we have an alternative to invasive tissue biopsy testing (which can be inadequate, expensive, less accessible, and difficult to repeat for disease surveillance).
A tissue sample had been taken from a patient in the U.S. state of Kansas to screen her for lung cancer. When her cancer required treatment and further investigation, taking a second sample from the same site was considered risky. A genomic liquid biopsy test offered doctors a non-invasive alternative to detect tumour abnormalities and determine treatment. He was found to carry actionable fusion in the ALK gene and would benefit with targeted treatment.
Liquid biopsy: A breakthrough in cancer treatment
In the last decade, there have been advances in genetic testing that could improve outcomes for patients. Liquid biopsy is one such breakthrough that will change the face of cancer treatment in India.
So, what is a liquid biopsy? Depending on the type of cancer, stage and clinical situation, the sample used for genomic profiling may vary. Among the available options, liquid biopsies are relatively new in India but can be used as an adjunct to conventional tumour biopsy for genomic testing. They can serve as a beneficial alternative, adjunct, or reflex to tumour biopsy for a particular clinical situation and offer significant advantages in some situations.
Sujata was diagnosed with lung adenocarcinoma with ROS1 fusion, and she was treated with a ROS1 inhibitor but relapsed. Since a repeat biopsy was not possible, the doctor recommended MedGenome’s LungTrackAdvance, an NGS-based liquid biopsy test. The accurate information from the test – the presence of a resistance mutation in the ROS1 gene – was used to provide her with an improved treatment plan.
The liquid biopsy test was first launched in India by MedGenome in 2018 and has already yielded tremendous results. The test is offered in India at a much lower price than in the US to make it more affordable. Not surprisingly, it is quickly becoming a popular tool for clinicians across the country.
How is liquid biopsy used for cancer care?
Genomic profiling based on liquid biopsies can be used to possibly:
- identify cancer
- develop treatment plans
- detect recurrences
- support monitoring of disease progression
- identify inherited genetic mutations and syndromes
The test looks for different types of genetic biomarkers in the cell-free DNA (cfDNA) that the tumor releases into the blood (ctDNA). Different biomarkers (SNVs, InDels, MSI, TMB) can be combined in a single test to increase predictive power. Example: ctDNA sequencing is used to detect resistant EGFR mutations in a case of recurrent lung cancer treated with EGFR TKI. A ctDNA- based genetic test is also used to detect resistance mutations in the ESR1 gene in breast cancer patients treated with hormone therapy. Similarly, it also helps in detecting driver mutations in various cancers as an adjunct or alternative to tumour biopsy.
In colorectal cancer patients, ctDNA-based tests help predict minimal residual disease (MRD) and risk of recurrence after surgery and therapy. The performance of these tests is now also being explored for the detection of relapse in lymphoma patients.
Analysis of genes involved in the homologous recombination repair (HRR) pathway, particularly BRCA1 and BRCA2, is important for making informed decisions about treatment and family counselling for patients with breast, ovarian, pancreatic, and prostate cancers. When tissue is not available, NGS-based genomic profiling on liquid biopsies allows detection of mutations in these 15 HRR genes.
The HRR-Track Liquid Biopsy test helped identify a pathogenic mutation in the BRCA2 gene in a 56-year-old man with acinar adenocarcinoma of the prostate, grade 5. This mutation in the BRCA2 gene was confirmed as a germline mutation in whole blood DNA, so genetic counselling was recommended. In addition, his treatment was tailored to this finding
Although molecular testing using tissue biopsies is the gold standard and is the first choice in the industry, liquid biopsy is emerging as the best alternative or complementary option. Some very compelling reasons become clearer when comparing the two options.
| Liquid Biopsy | Tissue Biopsy |
| Non-invasive/minimally invasive
Not painful, so resistance to taking the test is lower
|
More invasive, sometimes needing a surgical setting.
Reluctance to take the test because of the painful/tedious process |
| Can be performed repeatedly over the course of treatment | Not always possible to repeat this biopsy for clinical reasons or patient reservations |
| Can overcome tissue heterogeneity as it represents complete tumour profile. | Tissue samples may not contain all gene mutations as they are localised and therefore may give an incomplete picture |
| Can be used for early detection – detects disease progression before it shows up on scans/as clinical symptoms | Location of tumour needs to be known |
| Quick process with easy sample collection, allows for timely monitoring | Monitoring may not be as real-time |
| Convenient/non-surgical so the risk of complications is very low | There can be risk of complications due to location of the tumour or from the procedure itself |
| May use any of these – blood, CSF, pleural fluid, depending on type of cancer, clinical situation | Uses tissue sample from the cancerous part |
The future of liquid biopsy
Most liquid biopsy tests are based on genomics (examination of DNA in the blood for cancer related mutations), which has become increasingly important in the clinical setting over time and is increasingly used to guide treatment, especially in advanced stages of cancer. Liquid biopsy tests based on epigenomics (analysis of patterns of chemical marks – methylation signatures on DNA in blood) are in the development and validation phase and have yet to be used in the clinical setting for early cancer detection.
As part of the search for more efficient diagnostic and screening techniques, fragmentomics, which examines the pattern of the amount and size of DNA fragments in blood, is emerging as an actively pursued area of biomarker research. Both healthy and cancer cells release portions of their DNA (fragments) into the bloodstream. Fragmentomics can use these fragments to determine the tissue of origin and distinguish cancer-derived circulating DNA, overcoming the limitations of conventional methods. The ability to identify the tissue of origin would be very valuable for detecting cancer localisation and metastasis. In the future, this technique could become a more accurate and cost-effective alternative, ultimately monitoring the treatment of cancer patients after early detection of the disease.
References:
https://academic.oup.com/clinchem/article/66/12/1480/5998370
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027801/
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https://www.cancer.gov/news-events/cancer-currents-blog/2023/liver-cancer-liquid-biopsy-fragmentomics
https://www.mdpi.com/1422-0067/23/22/14197
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