Impact of tumor heterogeneity of driver mutation-positive lung cancer
Project/Area Number |
18K07271
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Wakayama Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
山本 信之 和歌山県立医科大学, 医学部, 教授 (60298966)
洪 泰浩 和歌山県立医科大学, 医学部, 准教授 (80426519)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | Liquid biopsy / EGFR遺伝子変異 / 肺癌 / リキッドバイオプシー / 非小細胞肺癌 / 分子標的治療薬 / heterogeneity |
Outline of Final Research Achievements |
In a multicenter study, we performed digital PCR analysis using tumor-derived DNA (cfDNA) in peripheral blood samples and showed that decline of cfDNA at 4 weeks was correlated with long-term efficacy (Akamatsu H, Lung Cancer 2019). We also reported that a variant of exon19 deletion affected the efficacy (Tokudome N, BMC Cancer 2020). We enrolled 94 cases in a prospective observational study and confirmed that the sensitivity of digital PCR and high-sensitivity next-generation sequencing was comparable using the first 12 samples. We are still working on the analysis, but it has been slightly slowed due to delays in the supplies caused by the COVID19 pandemic.
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Academic Significance and Societal Importance of the Research Achievements |
多施設共同研究の結果から、治療早期のcfDNA変化が長期治療効果を予測することを示した。また、従来一括りにされていたEGFR遺伝子変異陽性肺癌がバリアント部位によって異なる治療反応を示すことを報告した。 現在EGFR遺伝子変異陽性と診断された場合の治療法は均一であるが、こうした治療反応のばらつきを加味した場合、治療前や早期の段階でより強度の強い治療が必要になる集団(=早期に治療不応・耐性化する集団)を同定できる可能性がある。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Tumor mutation burden as a biomarker for lung cancer patients treated with pemetrexed and cisplatin (the JIPANG-TR).2020
Author(s)
Sakai K, Tsuboi M, Kenmotsu H, Yamanaka T, Takahashi T, Goto K, Daga H, Ohira T, Ueno T, Aoki T, Nakagawa K, Yamazaki K, Hosomi Y, Kawaguchi K, Okumura N, Takiguchi Y, Sekine A, Haruki T, Yamamoto H, Sato Y, Sugio K
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Journal Title
Cancer Sci.
Volume: 112(1)
Issue: 1
Pages: 388-396
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Heterogeneous Expression of Programmed Death Receptor-ligand 1 on Circulating Tumor Cells in Patients With Lung Cancer.2019
Author(s)
Koh H, Yagi S, Akamatsu H, Kanai K, Hayata A, Tokudome N, Akamatsu K, Higuchi M, Kanbara H, Nakanishi M, Ueda H, Yamamoto N.
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Journal Title
Clinical Lung Cancer
Volume: 印刷中
Issue: 4
Pages: 270-277.e1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Osimertinib for patients with EGFR T790M mutation-positive non-small-cell lung cancer and a poor performance status.2019
Author(s)
Nakashima K, Kimura M, Akamatsu H, Daga H, Imai H, Taira T, Ko R, Hisamatsu Y, Nishino K, Sugimoto T, Miyashita Y, Takahashi T.
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Journal Title
Jpn J Clin Oncol
Volume: 印刷中
Issue: 7
Pages: 671-675
DOI
Related Report
Peer Reviewed
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[Journal Article] Carboplatin Plus Nab-paclitaxel in Performance Status 2 Patients With Advanced Non-small-cell Lung Cancer.2019
Author(s)
Nakashima K, Akamatsu H, Murakami H, Niwa T, Iwamoto Y, Ozawa Y, Yokoyama T, Shoda H, Yamamoto N, Yoshioka H, Masuda K, Naito T, Mori K, Takahashi T.
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Journal Title
Anticancer Res.
Volume: 39
Issue: 3
Pages: 1463-1468
DOI
Related Report
Peer Reviewed
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[Journal Article] A Phase II Study of Gefitinib With Concurrent Thoracic Radiotherapy in Patients With Unresectable, Stage III Non-small-cell Lung Cancer Harboring EGFR Mutations (WJOG6911L).2019
Author(s)
Akamatsu H, Harada H, Tokunaga S, Yoshimura N, Ikeda H, Oizumi S, Sugimoto N, Takano T, Murakami H, Nishimura Y, Yamamoto N, Nakagawa K.
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Journal Title
Clinical Lung Cancer
Volume: 20
Issue: 1
Pages: e25-e27
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genetic Profiling of Non-Small Cell Lung Cancer at Development of Resistance to First- or Second-Generation EGFR-TKIs by CAPP-Seq Analysis of Circulating Tumor DNA.2019
Author(s)
Otsubo K, Sakai,K, Takeshita M, Harada D, Azuma K, Ota K, Akamatsu H, Goto K, Horiike A, Kurata T, Nakagaki N, Nosaki K, Iwama E, Nakanishi Y, Nishio N, Okamoto I.
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Journal Title
The Oncologist
Volume: 印刷中
Related Report
Peer Reviewed / Open Access
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[Journal Article] Exploration of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain reaction and next-generation sequencing.2018
Author(s)
Iwama E, Sakai K, Azuma K, Harada D, Nosaki K, Hotta K, Nishio M, Kurata T, Fukuhara T, Akamatsu H, Goto K, Shimose T, Kishimoto J, Nakanishi Y, Nishio K, Okamoto I.
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Journal Title
Cancer Sci
Volume: 109
Issue: 12
Pages: 3921-3933
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Erlotinib Plus Bevacizumab Phase II Study in Patients with Advanced Non-small-Cell Lung Cancer (JO25567): Updated Safety Results.2018
Author(s)
Kato T, Seto T, Nishio M, Goto K, Yamamoto N, Okamoto I, Tao L, Yu W, Khaznadar T, Tajima K, Shibata M, Seki A, Yamamoto N
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Journal Title
Drug Saf
Volume: 41
Issue: 2
Pages: 229-237
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Does EGFR Mutation Type Influence Patient-Reported Outcomes in Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer? Analysis of Two Large, Phase III Studies Comparing Afatinib with Chemotherapy (LUX-Lung 3 and LUX-Lung 6).2018
Author(s)
Wu YL, Hirsh V, Sequist LV, Hu CP, Feng J, Lu S, Huang Y, Schuler M, Mok T, Yamamoto N, O’Byrne K, Geater SL, Zhou C, Massey D, Marten A, Lungershausen J, Yang JC
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Journal Title
Patient
Volume: 11
Issue: 1
Pages: 131-141
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LuX-Lung 6, and LUX-Lung 7 Trials.2018
Author(s)
Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, Lee KH, Tsai CM, Kato T, Barrios CH, Schuler M, Hirsh V, Yamamoto N, O’Byrne K, Boyer M, Mok T, Peil B, Marten A, Chih-Hsin Yang J, Paz-Ares L, Park K
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Journal Title
Clinical Lung Cancer
Volume: 19
Issue: 4
Pages: e465-e479
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] HER2 missense mutations in breast cancer cells do not alter HER2 internalization or sensitivity to T-DM12020
Author(s)
Hiroaki Akamatsu, Rosa Mino, Marcel Mettlen, Dan Ye, Dhivya R. Sudhan, Albert Lin, Arnaldo Marin, Alberto Servetto, Kyung-min Lee, Sumanta Chatterjee, Sandra L. Schmid, Carlos L. Arteaga and Ariella B. Hanker
Organizer
AACR Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Predictive impact of sequential evaluation of PD-L1-expressing circulating tumor cells in NSCLC patients treated with nivolumab.2018
Author(s)
Koh Y, Akamatsu H, Mori K, Kanai K, Hayata A, Tokudome N, Higuchi M, Akamatsu K, Nakanishi M, Ueda H, Yamamoto N
Organizer
American Association for Cancer Research Annual Meeting
Related Report
Int'l Joint Research
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