实用肿瘤杂志2020年第35卷第3期 199 6展望 treatment-refractory, KRAS codon 12/13 wild-type. HER2-positive metastatic colorectal cancer(HERA 在结直肠癌患者中,HER2是一种临床相关的 CLES): a proof-of-concept, multicentre, open-label, 生物标志物。尽管其生存预后作用尚不确定,但临 phase 2 trial [J]. Lancet Oncol, 2016, 17(6):738-746. 床前及临床证据均支持HER2扩增或过表达是抗81 Meric-Bernstam F, Hurwitz H. Raghav KF,etal.Petr EGFR靶向治疗耐药的预测因子。目前HER2扩增 zumab plus trastuzumab for HER2-amplified metastate 或过表达的检测主要通过IHC、FISH和NGS,未 olorectal cancer(My Pathway): an updated report from 来液体活检或血浆 ctdnA测量有望成为新的手段。 centre, opel 近年来,临床试验结果表明,针对HER2的靶向 tudy [J]. Lancet Oncol, 2019, 20(4):518-530 [9] Sartore-Bianchi A Martino C. Lonardi S et al. Phase IT 治疗在约三分之一的HER2扩增或过表达结直肠 of pertuzumab and trastuzumab-emtansine(T-DM1) 癌患者中肿瘤退缩反应良好,且具有可耐受的安全 in patients with HER2-positive metastatic colorectal can- 性。目前还有众多的新型的针对HER2靶向药物如 The HERACLES-B(HER2 Amplification for Col- 抗体偶联药物(TDM-1和DS-8201)、新型TKIs orectaL cancer Enhanced Stratification, cohort B) trial [J] (来那替尼和突卡替尼)和HER2免疫治疗(疫苗 Ann OncoL, 2019. 30(suppl 5): v851-934 NK细胞和CAR-T细胞)都在积极研究。目前针101 Nakamura y, Okamoto w, Kato t. et aL. TrIUmPh:P- 对HER2扩增或过表达患者的治疗研究多样,而在 mary efficacy of a phase I trial of trastuzumab(T)and 结直肠癌患者中仍有2%左右的患者携带HER2基 因突变,这部分患者的治疗是否也对抗HER2靶向 cer(mCRC) with HER2 (ERBB2)amplification(amp) 治疗有效需要进一步探索。因此在何时检测HER2 in tumour tissue or circulating tumour DNA (ctDNA): A 状态以及用何种检测手段仍需要更多的研究去探 GOZILA suh-study [J]. Ann Oncol, 2019, 30(suppl 5 v198-252. 索,这或许对选择治疗方案顺序有着指示意义。未 Strickler JH, Zemla T.OuE,etal. Trastuzumab and tu 来,抗HER2治疗也可能会被运用到更早期的结直 catinib for the treatment of HER2 amplified metastatic 肠癌患者的全程治疗中去。 colorectal cancer(mCRC): Initial results from the MOUN TAINEER trial[J]. Ann Oncol, 2019. 30(suppl 5):v198- 参考文献 [1] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer inci- [12] Valtorta E, Martino C, Sartore-Bianchi A, et al. Assess- dence and mortality worldwide: sources, methods and ma- ment of a HER2 scoring system for colorectal cancer: jor patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015 results from a validation study [J]. Mod Pathol. 2015. 1365):359-386 28(11):1481-1491 [2] Weitz J. Koch M. Debus J et al. Colorectal cancer[Jl [13 Edenfield WJ. Chung KY. Gatalica Z. et al. Molecular Lancet,2004.365(9454:153-165 profiling of HER2-positive colorectal cancer for identifi- [3] Yarden Y. Sliwkowski MX Untangling the ErbB signaling cation of multiple potential drug targets [J]. J Clin Oncol. network [J]. Nat Rev Mol Cell Biol, 2001, 2(2):127-137. 2014.32( suppl I5:e14508 [4] Kim EK, Kim KA, Chang YL, et al. The frequency and [14] Missiaglia E, Jacobs B, D' Ario G, et al. Distal and proxi- clinical impact of HER2 alterations in lung adenocarci mal colon cancers differ in terms of molecular, patholog noma[. Plos one,2017,12(2):e0171280. ical, and clinical features [J]. Ann Oncol, 2014, 25(10) [5] Rakha EA. Pinder SE, Bartlett JM, et al. Updated UK rec- 1995-2001 ommendations for her2 assessment in breast [. [15] Kyung NS Sumi Y, Jiwon K, et al. BRAF PIK3CA and J Clin Pathol,2015,68(2):93-99 HER2 oncogenic alterations according to KRAs mutation [6 Richman SD Southward K. Chambers P et al. HER2 status in advanced colorectal cancers with distant metas overexpression and amplification as a potential therapeutic tasis[J]. Plos one,2016,113:e0151865 target in colorectal cancer: analysis of 3256 patients en- [16] Siena S, Sartore-Bianchi A, Trusolino L, et al. D01*Final rolled in the QUASAR, FOCUS and PICCOLO colorectal results of the HERACLES trial in HER2 amplified col- cancer trials[J]. J Pathol, 2016, 238(4):562-570 rectal cancer [J]. Ann Oncol, 2016, 27(suppl 4): iv30 [7] Sartore-Bianchi A, Trusolino L, Martino C, et al. Du- [17] Ross J, Ali S, Elvin J, et al. Targeted therapy for HER2 al-targeted therapy with trastuzumab and lapatinib in colorectal cancer [J]. J Clin Oncol, 2017, 35(suppl 15:3实用肿瘤杂志 2020 年 第 35 卷 第 3 期 www.syzlzz.com ·199· 6 展 望 在结直肠癌患者中，HER2 是一种临床相关的 生物标志物。尽管其生存预后作用尚不确定，但临 床前及临床证据均支持 HER2 扩增或过表达是抗 EGFR 靶向治疗耐药的预测因子。目前 HER2 扩增 或过表达的检测主要通过 IHC、FISH 和 NGS，未 来液体活检或血浆 ctDNA 测量有望成为新的手段。 近年来，临床试验结果表明，针对 HER2 的靶向 治疗在约三分之一的 HER2 扩增或过表达结直肠 癌患者中肿瘤退缩反应良好，且具有可耐受的安全 性。目前还有众多的新型的针对 HER2 靶向药物如 抗 体 偶 联 药 物（TDM-1 和 DS-8201）、 新 型 TKIs （来那替尼和突卡替尼）和 HER2 免疫治疗（疫苗、 NK 细胞和 CAR-T 细胞）都在积极研究。目前针 对 HER2 扩增或过表达患者的治疗研究多样，而在 结直肠癌患者中仍有 2% 左右的患者携带 HER2 基 因突变，这部分患者的治疗是否也对抗 HER2 靶向 治疗有效需要进一步探索。因此在何时检测 HER2 状态以及用何种检测手段仍需要更多的研究去探 索，这或许对选择治疗方案顺序有着指示意义。未 来，抗 HER2 治疗也可能会被运用到更早期的结直 肠癌患者的全程治疗中去。 参考文献 ： [1] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer inci￾dence and mortality worldwide: sources, methods and ma￾jor patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015, 136(5): 359-386. [2] Weitz J, Koch M, Debus J, et al. Colorectal cancer[J]. Lancet, 2004, 365(9454): 153-165. [3] Yarden Y, Sliwkowski MX. Untangling the ErbB signaling network[J]. Nat Rev Mol Cell Biol, 2001, 2(2): 127-137. [4] Kim EK, Kim KA, Chang YL, et al. The frequency and clinical impact of HER2 alterations in lung adenocarci￾noma[J]. Plos One, 2017, 12(2): e0171280. [5] Rakha EA, Pinder SE, Bartlett JM, et al. Updated UK rec￾ommendations for HER2 assessment in breast cancer[J]. J Clin Pathol, 2015, 68(2): 93-99. [6] Richman SD, Southward K, Chambers P, et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients en￾rolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials[J]. J Pathol, 2016, 238(4): 562-570. [7] Sartore-Bianchi A, Trusolino L, Martino C, et al. Du￾al-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERA￾CLES): a proof-of-concept, multicentre, open-label, phase 2 trial[J]. Lancet Oncol, 2016, 17(6): 738-746. [8] Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertu￾zumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study[J]. Lancet Oncol, 2019, 20(4): 518-530. [9] Sartore-Bianchi A, Martino C, Lonardi S, et al. Phase Ⅱ study of pertuzumab and trastuzumab-emtansine (T-DM1) in patients with HER2-positive metastatic colorectal can￾cer: The HERACLES-B (HER2 Amplification for Col￾orectaL cancer Enhanced Stratification, cohort B) trial[J]. Ann Oncol, 2019, 30 (suppl 5): v851-934. [10] Nakamura Y, Okamoto W, Kato T, et al. TRIUMPH: Pri￾mary efficacy of a phase Ⅱ trial of trastuzumab (T) and pertuzumab (P) in patients (pts) with metastatic colorectal cancer (mCRC) with HER2 (ERBB2) amplification (amp) in tumour tissue or circulating tumour DNA (ctDNA): A GOZILA sub-study[J]. Ann Oncol, 2019, 30 (suppl 5): v198-252. [11] Strickler JH, Zemla T, Ou F, et al. Trastuzumab and tu￾catinib for the treatment of HER2 amplified metastatic colorectal cancer (mCRC): Initial results from the MOUN￾TAINEER trial[J]. Ann Oncol, 2019, 30 (suppl 5): v198- 252. [12] Valtorta E, Martino C, Sartore-Bianchi A, et al. Assess￾ment of a HER2 scoring system for colorectal cancer: results from a validation study[J]. Mod Pathol. 2015, 28(11): 1481-1491. [13] Edenfield WJ, Chung KY, Gatalica Z, et al. Molecular profiling of HER2-positive colorectal cancer for identifi￾cation of multiple potential drug targets[J]. J Clin Oncol, 2014, 32(suppl 15):e14508. [14] Missiaglia E, Jacobs B, D'Ario G, et al. Distal and proxi￾mal colon cancers differ in terms of molecular, patholog￾ical, and clinical features[J]. Ann Oncol, 2014, 25(10): 1995-2001. [15] Kyung NS, Sumi Y, Jiwon K, et al. BRAF, PIK3CA, and HER2 oncogenic alterations according to KRAS mutation status in advanced colorectal cancers with distant metas￾tasis[J]. Plos One, 2016, 11(3): e0151865. [16] Siena S, Sartore-Bianchi A, Trusolino L, et al. D01*Final results of the HERACLES trial in HER2 amplified col￾orectal cancer[J]. Ann Oncol, 2016, 27(suppl 4): iv39. [17] Ross J, Ali S, Elvin J, et al. Targeted therapy for HER2 driven colorectal cancer[J]. J Clin Oncol, 2017, 35(suppl 15):3583