Globally, cancer ranks as the second leading cause of death. In India, the annual number of reported cancer cases is projected to increase from 14.6 lakh in 2022 to 17.3 lakh in 2025. Regrettably, experts estimate that a staggering 75 to 80 per cent of diagnosed individuals have advanced-stage tumors, posing challenges to treatment and resulting in less favorable outcomes.

Timing plays a crucial role in cancer management. A recent news report reveals that detecting cancer at Stage 1 provides an 85 percent chance of a cure, whereas with Stage 3 cancer, that percentage drops to approximately 30 percent. The increasing prevalence of cancer emphasizes the urgency for preventive diagnostics and precise cancer screening.

The Impact of Genetic Testing

The United States has achieved a 33 percent reduction in the cancer death rate since 1991, partly by implementing a combination of new treatments and screening measures.

Genetic testing, now available in India, is an exceptional new resource in our arsenal. It brings us one step closer to early diagnosis and screening, predicting disease progression (prognosis), and offering precision medicine options—tailored treatments that enhance patient outcomes.

With the introduction of cost-effective genomic testing in India, utilizing free-flowing DNA released from growing tumor tissue in the blood (liquid biopsy), we now have an alternative to invasive tissue biopsy testing. This liquid biopsy method addresses issues related to inadequacy, high cost, limited accessibility, and the difficulty of repeating the procedure for disease surveillance.

In a specific case from the U.S. state of Kansas, a patient underwent a tissue biopsy for lung cancer screening. However, due to the risks involved, obtaining a second tissue sample for further investigation and treatment was deemed unsafe. To overcome this challenge, doctors turned to genomic liquid biopsy testing, a non-invasive approach that could detect tumor abnormalities and guide treatment decisions. As a result, the patient was identified to have actionable fusion in the ALK gene, indicating a potential benefit from targeted treatment.

Liquid Biopsy: Latest Development in Cancer Treatment

In the last decade, significant progress has been made in genetic testing, holding the potential to enhance patient outcomes. Among these advancements, liquid biopsy stands out as a breakthrough that will revolutionize cancer treatment in India.

What is liquid biopsy? The choice of sample for genomic profiling may vary depending on factors such as the type and stage of cancer, as well as the clinical context. Liquid biopsies are a relatively new option in India but can be used alongside traditional tumor biopsies for genomic testing. They serve as a valuable alternative, complement, or reflex to tumor biopsies in specific clinical scenarios, offering notable advantages in certain situations.

Sujata received a diagnosis of lung adenocarcinoma with ROS1 fusion, and her initial treatment involved a ROS1 inhibitor. However, she experienced a relapse, and conducting a repeat biopsy was not feasible. In such a situation, the doctor recommended MedGenome's LungTrackAdvance, a liquid biopsy test based on next-generation sequencing (NGS). This test provided accurate information, revealing the presence of a resistance mutation in the ROS1 gene. The results were instrumental in devising an improved treatment plan for Sujata.

MedGenome introduced the liquid biopsy test to the Indian market in 2018, and it has already showcased remarkable outcomes. The laboratory-developed test adheres to global standards, being CAP-accredited with extensive validation. Moreover, the company has ensured that the test remains affordable in India, offering it at a significantly lower price compared to the US. Unsurprisingly, this test has gained rapid popularity among clinicians throughout the country.

How does Liquid Biopsy Help with Cancer Treatment?

Based on liquid biopsies, genomic profiling may be used to:

• Identify cancer
• Develop treatment plans
• Detect recurrences
• Support monitoring progression of the disease
• Identify inherited genetic mutations and syndromes

The test examines various genetic biomarkers present in the cell-free DNA (cfDNA) released by the tumor into the bloodstream (ctDNA). Different biomarkers, such as SNVs, InDels, MSI, and TMB, can be combined within a single test to enhance its predictive capability. For instance, ctDNA sequencing is employed to identify resistant EGFR mutations in cases of recurrent lung cancer that have undergone EGFR TKI treatment. Additionally, a ctDNA-based genetic test is utilized to detect resistance mutations in the ESR1 gene among breast cancer patients undergoing hormone therapy. Moreover, the test serves as a valuable adjunct or alternative to tumor biopsies, aiding in the detection of driver mutations in various types of cancer.

CtDNA-based tests play a crucial role in predicting minimal residual disease (MRD) and the risk of recurrence after surgery and therapy in colorectal cancer patients. Furthermore, researchers are now investigating the performance of these tests in detecting relapse among lymphoma patients.

In patients with breast, ovarian, pancreatic, and prostate cancers, analyzing genes related to the homologous recombination repair (HRR) pathway, particularly BRCA1 and BRCA2, holds significance for treatment decisions and family counseling. When tissue samples are unavailable, NGS-based genomic profiling on liquid biopsies enables the identification of mutations in these 15 HRR genes, facilitating informed decision-making.

The HRR-Track Liquid Biopsy test played a pivotal role in identifying a pathogenic mutation in the BRCA2 gene in a 56-year-old man diagnosed with grade 5 acinar adenocarcinoma of the prostate. The presence of this mutation was further confirmed as a germline mutation through analysis of whole blood DNA, leading to a recommendation for genetic counseling. Furthermore, his treatment plan was tailored based on this significant finding.

Although molecular testing using tissue biopsies remains the gold standard and the preferred choice in the industry, liquid biopsy is emerging as a highly valuable alternative or complementary option.

A comparison between the two approaches highlights several compelling reasons in favor of liquid biopsy.

Future of Liquid Biopsy

Genomics forms the basis of most liquid biopsy tests, wherein DNA in the blood is examined for cancer-related mutations. The clinical importance of genomics has been increasing over time, and it is increasingly used to guide treatment, particularly in advanced stages of cancer. Liquid biopsy tests that rely on epigenomics, which involves analyzing patterns of chemical marks (methylation signatures) on DNA in the blood, are currently being developed and validated but have not yet been employed in the clinical setting for early cancer detection.

As researchers seek more efficient diagnostic and screening techniques, they are actively pursuing fragmentomics as a promising area of biomarker research. Fragmentomics examines the pattern of the quantity and size of DNA fragments in the blood. Both healthy and cancer cells release fragments of their DNA into the bloodstream. By utilizing these fragments, fragmentomics can determine the tissue of origin and differentiate cancer-derived circulating DNA, thus overcoming the limitations of conventional methods.

The ability to identify the tissue of origin would be highly valuable in detecting the localization and metastasis of cancer. In the future, this technique could potentially become a more accurate and cost-effective alternative, enabling the monitoring of cancer patients' treatment following the early detection of the disease.

Resource -  https://www.expresshealthcare.in/news/liquid-biopsy-promising-diagnostic-tool-in-clinical-oncology/439754/

Authored by- Dr Suruchi Aggarwal, Ph.D. (Human Genomics), Lead, Scientific Affairs & Technical Support – Oncology, MedGenome