2021 Fiscal Year Final Research Report
Detection of acquired resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer using circulating tumor DNA
| Project/Area Number |
17K10625
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
高橋 直樹 地方独立行政法人埼玉県立病院機構埼玉県立がんセンター(臨床腫瘍研究所), 病院 消化器内科, 医長 (20744204)
澤田 武 金沢大学, 附属病院, 医員 (60345626)
|
|---|
| Project Period (FY) |
2017-04-01 – 2022-03-31
|
| Keywords | 循環腫瘍DNA / 大腸癌 / 上皮成長因子受容体 / 遺伝子変異 / 個別化治療 |
|---|
| Outline of Final Research Achievements |
Circulating tumor DNA (ctDNA) has been attracting attention for its ability to provide comprehensive, minimally invasive tissue profiling. To assess clinical usefulness of ctDNA as prognostic and predictive marker for the treatment of metastatic colorectal cancer (mCRC), we explored genetic alterations in ctDNA in 50 patients with RAS wildtype mCRC treated with anti-EGFR antibodies. Blood samples were collected before initiation and during administration of anti-EGFR antibodies as well as after disease progression (PD). Extraction of ctDNA from plasma and detection of genetic changes associated with resistance to anti-EGFR antibodies were performed by digital PCR. For patients with genetic alteration identified before chemotherapy or after PD, we also performed analysis of ctDNA during the course of the disease. Analyses are ongoing to determine if ctDNA can be used to predict response to EGFR blockade before treatment, as well as to monitor disease response during EGFR blockade.
|
| Free Research Field |
下部消化管
|
| Academic Significance and Societal Importance of the Research Achievements |
今後解析を進めることにより、切除不能進行再発大腸癌に対する抗EGFR抗体薬投与前に、RAS以外の遺伝子異常が予後不良因子となり得るか、またどの程度の変異アレルで治療無効と予測可能かの知見を蓄積できる。それにより、抗EGFR抗体薬の適応判定および治療効果予測をより精密に行うことが可能となる。また、抗EGFR抗体投与後に、耐性因子と想定される（複数の）遺伝子異常がどのタイミングで検出されるかの新たな知見を得ることができる。それをもとに、ctDNAによる治療標的の同定と治療効果のモニタリングを目的とした繰り返し実施可能な低侵襲検査が提案できる。
|
