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Saliva EFIRM Liquid Biopsy

Monday, 18 March 2024 at 16:00

Add to Calendar ▼2024-03-18 16:00:002024-03-18 17:00:00Europe/LondonSaliva EFIRM Liquid BiopsyEmerging Technologies and Paradigms for In Vitro Dx Europe 2024 in Rotterdam, The NetherlandsRotterdam, The NetherlandsSELECTBIOenquiries@selectbiosciences.com

Circulating free DNA (ctDNA) liquid biopsy is rapidly emerging to address the unmet clinical need to detect signature mutations in human cancer based on cell-free circulating tumor DNA (ctDNA) as a surrogate for the tumor genome. The detection of ctDNA via liquid biopsy will facilitate analysis of tumor genomics needed for early detection, molecular targeted therapy, treatment monitoring, onset of acquired resistance mutations, recurrence and minimal residual diseases. Currently, most liquid biopsy approaches are plasma-based using PCR and/or next generation sequencing (NGS) with performance concordance in the 60-70% range compared with biopsy-based genotyping. The exciting horizon ctDNA liquid biopsy is hampered by low copy number of ctDNA, volume requirement for assays and sensitivity of detection platform. Saliva is a bodily fluid that we produce ~600ml per day and harbors multiple omics constituents, including ctDNA that can be harnessed non-invasive for personalized and precision medicine applications, is ideal for ctDNA liquid biopsy. Yet conventional PCR-based technologies cannot detect ctDNA in saliva samples whereas an emerging liquid biopsy platform “Electric Field Induced Release and Measurement (EFIRM)” consistently detect ctDNA from NSCLC patients with actionable mutations in plasma and saliva with concordance of 95%+ with tissue/biopsy-based genotyping including early-stage lesions. EFIRM provides the most accurate targeted detection that can assist clinical treatment decisions for non-small cell lung cancer (NSCLC), with tyrosine kinase inhibitors (TKI) that can extend the disease progress free survival period of these patients. The mechanism of EFIRM for ctDNA detection was recently revealed to detect ctDNA that are ~45 bp single-stranded ctDNA we termed ultra-short ctDNA (usctDNA), whereas the conventional ctDNA are mononucleosomal that are ~160 bp and double-stranded. Conventional ddPCR or NGS cannot detect usctDNAs, where a minimum of 78-bp is needed for amplification. Custom design of ddPCR assay to quantify the EGFR L858R usctDNA in saliva of NSCLC patients revealed that the usctDNA is present at high abundance, mean= 62,636; SD ± 63,334, range: 16,500 to 56,375 copies per mL of saliva, permitting its detection in small saliva volume of 50uL or less, directly without sample processing. These results led to the conclusion that there is an emerging landscape of usctDNA that is present at much higher stoichiometry than mononucleosomal ctDNA permitting detection by the EFIRM technology in micro-litter volume of saliva samples, directly without processing, presenting a new frontier for ctDNA liquid biopsy, addressing the low copy number and limit of detection bottleneck of mnctDNA liquid biopsy.