VI．進行再発大腸癌に対する新規分子標的薬の開発
本邦にて大腸癌に用いる分子標的薬としてベバシズマブ（抗VEGF抗体薬），セツキシマブ/パニツムマブ（抗EGFR抗体薬），そしてレゴラフェニブ，ラムシルマブ，アフリベルセプトが使用されている．Precision Medicineにて，各遺伝子異常をターゲットとした新規分子標的薬の開発が進んでいる．大腸癌に関しては，特にHER2とBRAFを標的としたHER2，BRAF，MEKに対する分子標的薬の有効な結果がでている．HER2陽性KRAS野生型大腸癌に対してHER2の2重ターゲット療法が有効な治療であることが報告された．また，BRAF V600E遺伝子変異陽性大腸癌に対し，BRAF阻害剤+抗EGFR...
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| Published in | 日本大腸肛門病学会雑誌 Vol. 71; no. 10; pp. 417 - 424 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本大腸肛門病学会
2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0047-1801 1882-9619 |
| DOI | 10.3862/jcoloproctology.71.417 |
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| Abstract | 本邦にて大腸癌に用いる分子標的薬としてベバシズマブ（抗VEGF抗体薬），セツキシマブ/パニツムマブ（抗EGFR抗体薬），そしてレゴラフェニブ，ラムシルマブ，アフリベルセプトが使用されている．Precision Medicineにて，各遺伝子異常をターゲットとした新規分子標的薬の開発が進んでいる．大腸癌に関しては，特にHER2とBRAFを標的としたHER2，BRAF，MEKに対する分子標的薬の有効な結果がでている．HER2陽性KRAS野生型大腸癌に対してHER2の2重ターゲット療法が有効な治療であることが報告された．また，BRAF V600E遺伝子変異陽性大腸癌に対し，BRAF阻害剤+抗EGFR抗体薬+MEK阻害剤の3剤併用療法が有効であることが報告された．遺伝子異常別にそれらを標的とした治療の開発が今後更に進み，個々の患者にあった個別化治療を行うことで，更なる治療成績の向上を期待したい． |
|---|---|
| AbstractList | 本邦にて大腸癌に用いる分子標的薬としてベバシズマブ（抗VEGF抗体薬），セツキシマブ/パニツムマブ（抗EGFR抗体薬），そしてレゴラフェニブ，ラムシルマブ，アフリベルセプトが使用されている．Precision Medicineにて，各遺伝子異常をターゲットとした新規分子標的薬の開発が進んでいる．大腸癌に関しては，特にHER2とBRAFを標的としたHER2，BRAF，MEKに対する分子標的薬の有効な結果がでている．HER2陽性KRAS野生型大腸癌に対してHER2の2重ターゲット療法が有効な治療であることが報告された．また，BRAF V600E遺伝子変異陽性大腸癌に対し，BRAF阻害剤+抗EGFR抗体薬+MEK阻害剤の3剤併用療法が有効であることが報告された．遺伝子異常別にそれらを標的とした治療の開発が今後更に進み，個々の患者にあった個別化治療を行うことで，更なる治療成績の向上を期待したい． |
| Author | 吉田, 和弘 高橋, 孝夫 松橋, 延壽 |
| Author_xml | – sequence: 1 fullname: 高橋, 孝夫 organization: 岐阜大学大学院医学系研究科腫瘍制御学講座腫瘍外科学分野 – sequence: 1 fullname: 松橋, 延壽 organization: 岐阜大学大学院医学系研究科腫瘍制御学講座腫瘍外科学分野 – sequence: 1 fullname: 吉田, 和弘 organization: 岐阜大学大学院医学系研究科腫瘍制御学講座腫瘍外科学分野 |
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| References | 15) Van Cutsen E, Cuyle p-J, Huijberts S, et al: BEACON CRC study safety lead-in (SLI) in patients with BRAFV600E metastatic colorectal cancer (mCRC): Efficacy and tumor markers. J Clin Oncol 36:Abstract No. 520, 2018 14) van Geel RM, Tabernero J, Elez E, et al: A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer. Cancer Discov 7:610-619, 2017 18) Vassal G, Moro-sibilot D, Le Deley MC, et al: Biomarker-driven access to crizotinib in ALK, MET or ROS1 positive(+) malignancies in adults and children: The French national AcSe Program. Eur J Cancer 51:Abstract No. 12LBA, 2015 2) Siena S, Sartore-Bianchi A, Marsoni S, et al: Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Annals of Oncology 29:1108-1119, 2018 8) Hyman DM, Puzanov I, Subbiah V, et al: Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med 373:726-736, 2015 11) Corcoran RB, André T, Atreya CE, et al: Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAFV600E-Mutant Colorectal Cancer. Cancer Discov 8:428-443, 2018 17) Jonker DJ, Nott LM, Yoshino T, et al: A phase III randomized study of napabucasin [BBI608] (NAPA) vs placebo (PBO) in patients (Pts) with pretreated advanced colorectal carcinoma (ACRC): CCTG/AGITG CO. 23 trial: Ann Oncol 27:Abstract No. 4540, 2016 4) Hainsworth JD, Meric-Bernstam F, Swanton C, et al: Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from MyPathway, an open-label, phase IIa multiple basket study. J Clin Oncol 36:536-542, 2018 12) Kopetz S, McDonough SL, Lenz H-l, et al: Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406). J Clin Oncol 35:Abstract No. 3505, 2017 13) Kopetz S, McDonough SL, Morris VK, et al: Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406). J Clin Oncol 35:Abstract No. 520, 2017 16) Cremolini C, Di Bartolomeo M, Amatu A, et al: BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann Oncol 26:2092-2097, 2015 9) Yaeger R, Cercek A, O'Reilly EM, et al: Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients. Clin Cancer Res 21:1313-1320, 2015 7) Kopetz S, Desai J, Chan E, et al: Phase II Pilot Study of vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer. J Clin Oncol 33:4032-4038, 2015 6) Falchook GS, Long GV, Kurzrock R, et al: Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumors: a phase 1 dose-escalation trial. Lancet 379:1893-1901, 2012 1) Dienstmann R, Salazar R, Tabernero J: The evolution of our molecular understanding of colorectal cancer: what we are doing now, what the future holds, and how tumor profiling is just the beginning. Am Soc Clin Oncol Educ Book:91-99, 2014 5) Hurwitz H, Raghav KPS, Burris HA, et al: Pertuzumab+trastumab for HER2-amplified/overexpressed metastatic colorectal cancer (mCRC): Interim data from MyPathway. J Clin Oncol 35:Abstract No. 676, 2017 10) Corcoran RB, Atreya CE, Falchook GS, et al: Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer. J Clin Oncol 33:4023-4031, 2015 3) Sartore-Bianchi A, Trusolino L, Martino C, et al: Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicenter, open-label, phase 2 trial. Lancet Oncology 17:738-746, 2016 |
| References_xml | – reference: 7) Kopetz S, Desai J, Chan E, et al: Phase II Pilot Study of vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer. J Clin Oncol 33:4032-4038, 2015 – reference: 11) Corcoran RB, André T, Atreya CE, et al: Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAFV600E-Mutant Colorectal Cancer. Cancer Discov 8:428-443, 2018 – reference: 4) Hainsworth JD, Meric-Bernstam F, Swanton C, et al: Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from MyPathway, an open-label, phase IIa multiple basket study. J Clin Oncol 36:536-542, 2018 – reference: 1) Dienstmann R, Salazar R, Tabernero J: The evolution of our molecular understanding of colorectal cancer: what we are doing now, what the future holds, and how tumor profiling is just the beginning. Am Soc Clin Oncol Educ Book:91-99, 2014 – reference: 18) Vassal G, Moro-sibilot D, Le Deley MC, et al: Biomarker-driven access to crizotinib in ALK, MET or ROS1 positive(+) malignancies in adults and children: The French national AcSe Program. Eur J Cancer 51:Abstract No. 12LBA, 2015 – reference: 12) Kopetz S, McDonough SL, Lenz H-l, et al: Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406). J Clin Oncol 35:Abstract No. 3505, 2017 – reference: 13) Kopetz S, McDonough SL, Morris VK, et al: Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406). J Clin Oncol 35:Abstract No. 520, 2017 – reference: 3) Sartore-Bianchi A, Trusolino L, Martino C, et al: Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicenter, open-label, phase 2 trial. Lancet Oncology 17:738-746, 2016 – reference: 17) Jonker DJ, Nott LM, Yoshino T, et al: A phase III randomized study of napabucasin [BBI608] (NAPA) vs placebo (PBO) in patients (Pts) with pretreated advanced colorectal carcinoma (ACRC): CCTG/AGITG CO. 23 trial: Ann Oncol 27:Abstract No. 4540, 2016 – reference: 14) van Geel RM, Tabernero J, Elez E, et al: A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer. Cancer Discov 7:610-619, 2017 – reference: 8) Hyman DM, Puzanov I, Subbiah V, et al: Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med 373:726-736, 2015 – reference: 2) Siena S, Sartore-Bianchi A, Marsoni S, et al: Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Annals of Oncology 29:1108-1119, 2018 – reference: 15) Van Cutsen E, Cuyle p-J, Huijberts S, et al: BEACON CRC study safety lead-in (SLI) in patients with BRAFV600E metastatic colorectal cancer (mCRC): Efficacy and tumor markers. J Clin Oncol 36:Abstract No. 520, 2018 – reference: 5) Hurwitz H, Raghav KPS, Burris HA, et al: Pertuzumab+trastumab for HER2-amplified/overexpressed metastatic colorectal cancer (mCRC): Interim data from MyPathway. J Clin Oncol 35:Abstract No. 676, 2017 – reference: 16) Cremolini C, Di Bartolomeo M, Amatu A, et al: BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann Oncol 26:2092-2097, 2015 – reference: 6) Falchook GS, Long GV, Kurzrock R, et al: Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumors: a phase 1 dose-escalation trial. Lancet 379:1893-1901, 2012 – reference: 10) Corcoran RB, Atreya CE, Falchook GS, et al: Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer. J Clin Oncol 33:4023-4031, 2015 – reference: 9) Yaeger R, Cercek A, O'Reilly EM, et al: Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients. Clin Cancer Res 21:1313-1320, 2015 |
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| SubjectTerms | BRAF HER2 MEK 大腸癌化学療法 新規分子標的薬 |
| Title | VI．進行再発大腸癌に対する新規分子標的薬の開発 |
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