by Introduction to Liquid Biopsy through Cell-Free DNA
Liquid biopsy is an emerging non-invasive method to detect cancer. It analyzes circulating cell-free tumor DNA (ctDNA) from blood samples of cancer patients. ctDNA originates from tumor cells that undergo apoptosis or necrosis and get released into the bloodstream. These fragmented ctDNA enter the circulating blood and can be isolated and analyzed.
Detection of ctDNA
ctDNA concentrations in blood are usually very low, ranging from 0.01% to 10% of the total circulating cell-free DNA. Advanced techniques like digital PCR and next generation sequencing are used for detecting these low levels of ctDNA. Digital PCR has high sensitivity and can detect even single-copy mutations. Next generation sequencing allows profiling of hundreds of genes simultaneously. Using personalized genetic signatures, ctDNA from individual patient’s tumor can be distinguished from normal cell-free DNA.
Clinical Applications of ctDNA Analysis
Monitoring cancer progression: Changes in Circulating Cell-Free Tumor DNA levels reflect tumor dynamics and can be used for disease monitoring. Rising ctDNA levels indicate disease progression while falling levels suggest response to treatment. It allows frequent, non-invasive monitoring without repeated biopsies.
Detecting residual and recurrent disease: ctDNA analysis can detect residual cancer cells that persist after primary treatment and help in early detection of recurrence. This makes curative surgery or localized therapies possible in recurrent settings.
Guiding treatment decisions: Detecting mutations in ctDNA guides targeted therapy choices. Changes in mutant allele fractions during treatment help assess response in real-time and guide switching to alternative regimens.
Screening and early detection: Specific ctDNA alterations can potentially be detected even before tumors are clinically apparent, allowing for earlier cancer detection. Large screening studies are ongoing to evaluate the clinical utility of ctDNA screening.
Challenges and Circulating Cell-Free Tumor DNA
Analytical sensitivity still lags behind tissue biopsy based methods. Multiple mutant copies may be needed for consistent ctDNA detection. Assay requirements also vary between cancer types based on DNA release dynamics. Distinguishing low levels of ctDNA from background noise is challenging. Standardization of pre-analytical variables like sample collection is needed.
studies integrating ctDNA and imaging will provide comprehensive care. Combining with additional liquid biopsy components like exosomes will give broader biological insights. Large prospective validation studies are warranted before guiding clinical management decisions solely based on ctDNA analysis. With continued technical advances, liquid biopsy holds promise to revolutionize cancer screening, monitoring and treatment
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
About Author - Ravina Pandya
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