Research for detecting and overcoming multidrug resistance caused by EGFR-C797S/T790M mutation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15936
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: UCHIBORI Ken 公益財団法人がん研究会, 有明病院 呼吸器内科, 医長 (40633053)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: EGFR遺伝子変異 / EGFR阻害剤 / Osimertinib / C797S変異 / 薬剤耐性

Outline of Final Research Achievements

We investigated a highly sensitive method for detecting EGFR mutations in plasma cfDNA using droplet digital PCR, and confirmed the appearance of T790M/C797S in some patients who developed resistance to osimertinib treatment after T790M. Moreover, we found that our ddPCR system is expected to be a method for recognizing signs of drug resistance earlier than imaging.
In December 2020, a multi-center Phase I/II study of brigatinib plus panitumumab combination therapy for C797S-resistant mutation-positive advanced EGFR lung cancer (AMED Innovative Cancer Research) started and is now underway. We believe that the above findings will be of great benefit to the applicant in our role as an investigator.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

EGFR阻害剤による肺癌治療は、患者ごとの最適化治療が急速に進歩しているとともに、耐性出現後の克服法の重要性が非常に大きくなっている。現在EGFR阻害剤として最も重要視されるのはosimerinibであるが、本研究によりosimertinib耐性を生じるC797S変異を血漿から検出可能であることを検出でき、CTなどによる標準的な効果判定よりも早期に耐性を予見できたことは大きな意味を持つ。すなわち、osimertinib後の治療開発を進めるにあたり、対象となる症例を簡便かつ正確に抽出できる手法の確立に貢献すると期待される。