EXPANDING PRECISION MEDICINE: DIGITAL-PCR IN LIQUID BIOPSIES TO IMPROVE NSCLC PATIENTS’ FOLLOW-UP

EUGENIA COSTARELLI; ALEJANDRO SOLA; MAYORGA LIA; BRANHAM MARÍA TERESITA; LAURITO SERGIO; MARÍA ROQUÉ; REAL SEBASTIAN

Mar del plata

Congreso; Reunión Anual de la sociedad argentina de investigación clínica; 2023

Although precision medicine has significantly improved the life ex- pectancy of cancer patients, a major challenge lies in its heavy reli- ance on next-generation sequencing (NGS), which is expensive and scarcely accessible in Argentina. Another obstacle is the low sensi- tivity of the techniques used for treatment follow-up, therefore ther- apeutic failure detection arrives late, when metastases is already present. Our aim is to improve the monitoring of NSCLC patients by determining biomarkers through liquid biopsies and digital PCR (ddPCR), a highly sensitive and cost-effective detection method. Here we present the validation and set up of the tool. Objectives: 1-Develop a methodology for treatment response monitoring to EGFR inhibitors (EGFRi) using liquid biopsy-based tumor burden analysis. 2-Generate detection panels for resistance mutations to EGFRi. Description & validation: 1-For tracking response to EGFRi, we analyzed in blood samples, the quantitative changes over time in the two main EGFR biomarkers (BM), L858R and 18 different dele- tionsofexon-19.QuantitativechangesintheBMreflectedwhether the tumor is responding well (decrease), partially (stable), or if it is resistant to the therapy (increase). This will enable early anticipation of disease progression and provide a rapid parameters for treatment management. We used an in vivo xenograft model to validate the correlation between tumor burden and BM’ concentration. 2-We generated three ddPCR panels to detect the major mutations that lead to EGFRi resistance: a.On-target EGFR mutations T790M and S797X; b.BRAF V600E and PI3K E545K; c.CNV of EGFR, HER2, and MET. We have confirmed the proper detection of each BM using liquid biopsy. This approach will offer an affordable tool to person- alized therapies based on identified mutations, enabling broader, earlier, and proactive management of available therapeutic options. With these tools we expect to contribute to the improvement of pa- tient treatment outcomes.