2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.06B.17 Detection of EGFR Mutations T790M and L858R for Therapeutic Guidance of NSCLC

Pdf Summary

The document discusses the detection of two specific EGFR mutations, T790M and L858R, which are pivotal for guiding therapy in non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of lung cancer cases, which resulted in approximately 2.5 million new cases and 1.8 million deaths in 2022. EGFR mutations contribute to resistance against tyrosine kinase inhibitors (TKIs), particularly through mutations in exon 19, 20 (T790M), or 21 (L858R).<br /><br />The study introduces a novel assay employing a strain-promoted alkyne-azide cycloaddition (SPAAC) ligation method to detect these mutations in circulating tumor DNA (ctDNA). Key features of the assay include high sensitivity, capable of detecting mutations down to 1 copy/µL, which aligns with the capabilities of droplet digital PCR (ddPCR). The assay also boasts a high specificity, achieving a 90% suppression of wild-type DNA, ensuring that the detection focuses on the mutant genotypes.<br /><br />Clinical samples were tested, demonstrating the assay's proficiency in identifying L858R and T790M mutations at various lung cancer stages, potentially aiding in monitoring treatment resistance. The assay operates efficiently with a processing time of about two hours.<br /><br />Future directions for this research include further streamlining the assay to decrease the processing time and expanding testing across additional clinical cohorts to reinforce validation. The document underscores the importance of these advancements for improving therapeutic decision-making in NSCLC, ultimately aiming to enhance patient outcomes through better management of TKI resistance.

Asset Subtitle

Shima Asil

Meta Tag

Speaker Shima Asil

Topic Pathology and Biomarkers

Keywords

EGFR mutations

T790M

L858R

NSCLC

lung cancer

tyrosine kinase inhibitors

circulating tumor DNA

SPAAC ligation

ddPCR

treatment resistance