Acquired resistance mechanism to EGFR-TKI using circulating cell-free tumor DNA

Research Project

Project/Area Number	15K21526
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Tumor diagnostics Tumor therapeutics
Research Institution	Kindai University
Principal Investigator	KANEDA Hiroyasu 近畿大学, 医学部, 講師 (50351599)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	バイオマーカー / 分子標的治療 / 血漿DNA / EGFR遺伝子変異陽性肺がん / EGFRチロシンキナーゼ阻害剤耐性 / 耐性克服 / Digital PCR
Outline of Final Research Achievements	We evaluated liquid biopsy assays by digital PCR for detection of T790M mutations of EGFR in EGFR mutation-positive NSCLC patients with acquired EGFR-TKI resistance.Plasma samples from 34 patients including 13 paired samples who developed progression during EGFR-TKI treatment were collected. Samples were deemed to be ddPCR-positive if more than 0.015% of mutant allele frequency in cell-free DNA. All plasma samples were genotyped successfully. For 13 paired samples, TKI-sensitizing and T790M mutations were detected in plasma of 13 (100%) and 10 (76%) patients, respectively. T790M mutation was detected in one patient with pretreatment plasma sample.Noninvasive genotyping ddPCR assay revealed that T790M was found in the majority of NSCLC patients who developed progression on EGFR-TKI.