Wu Yeming.Arrival of the era of pan-tumor targeted drugs for children represented by TRK inhibitors[J].Journal of Clinical Pediatric Surgery,2023,22(07):607-610.[doi:10.3760/cma.j.cn101785-202303020-002]
迎接以TRK抑制剂为代表的儿童泛肿瘤靶向药物时代的到来
- Title:
- Arrival of the era of pan-tumor targeted drugs for children represented by TRK inhibitors
- 关键词:
- 受体酪氨酸激酶样孤儿受体; 肿瘤; 分子靶向治疗; 外科手术; 儿童
- Keywords:
- Receptor Tyrosine Kinase-like Orphan Receptors; Neoplasms; Molecular Targeted Therapy; Surgical Procedures; Operative; Child
- 摘要:
- 随着精准医学的发展，针对儿童晚期恶性实体瘤的免疫治疗和分子靶向药物治疗已开始应用于临床。以原肌球蛋白受体激酶（tropomyosin-receptor kinase，TRK）抑制剂拉罗替尼和恩曲替尼为代表的靶向治疗药物对各类神经营养因子受体酪氨酸激酶（neurotrophin tyrosine receptor kinase，NTRK）基因融合阳性表达的儿童晚期恶性实体瘤具有较高的有效性和安全性，标志着"儿童泛肿瘤靶向药物时代"的到来。本文旨在介绍此类药物的作用机制及其临床应用研究进展。
- Abstract:
- With a rapid development of precision medicine, immunotherapy and molecular targeted drug dosing for advanced malignant solid tumors have been applied in children.Among them, the effectiveness and safety of TRK inhibitors larotrectinib and entrectinib in children with advanced malignant solid tumors with positive expressions of various NTRK fusion genes marks the arrival of the era of pan-tumor targeted drugs for children.This review focused upon the mechanisms and clinical research advances of these drugs.
参考文献/References:
[1] Gr?bner SN, Worst BC, Weischenfeldt J, et al.The landscape of genomic alterations across childhood cancers[J].Nature, 2018, 555(7696):321-327.DOI:10.1038/nature25480.
[2] Ma XT, Liu Y, Liu YL, et al.Pan-cancer genome and transcriptome analyses of 1, 699 paediatric leukaemias and solid tumours[J].Nature, 2018, 555(7696):371-376.DOI:10.1038/nature25795.
[3] Harris MH, DuBois SG, Glade Bender JL, et al.Multicenter feasibility study of tumor molecular profiling to inform therapeutic decisions in advanced pediatric solid tumors:the individualized cancer therapy (iCat) study[J].JAMA Oncol, 2016, 2(5):608-615.DOI:10.1001/jamaoncol.2015.5689.
[4] Allen CE, Laetsch TW, Mody R, et al.Target and agent prioritization for the children’s oncology group-national cancer institute pediatric MATCH trial[J].J Natl Cancer Inst, 2017, 109(5):djw274.DOI:10.1093/jnci/djw274.
[5] Gatalica Z, Xiu J, Swensen J, et al.Molecular characterization of cancers with NTRK gene fusions[J].Mod Pathol, 2019, 32(1):147-153.DOI:10.1038/s41379-018-0118-3.
[6] Pulciani S, Santos E, Lauver AV, et al.Oncogenes in solid human tumours[J].Nature, 1982, 300(5892):539-542.DOI:10.1038/300539a0.
[7] Martin-Zanca D, Hughes SH, Barbacid M.A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences[J].Nature, 1986, 319(6056):743-748.DOI:10.1038/319743a0.
[8] Vaishnavi A, Capelletti M, Le AT, et al.Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer[J].Nat Med, 2013, 19(11):1469-1472.DOI:10.1038/nm.3352.
[9] Forsythe A, Zhang W, Phillip Strauss U, et al.A systematic review and meta-analysis of neurotrophic tyrosine receptor kinase gene fusion frequencies in solid tumors[J].Ther Adv Med Oncol, 2020, 12:1758835920975613.DOI:10.1177/1758835920975613.
[10] Westphalen CB, Krebs MG, Le Tourneau C, et al.Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population[J].NPJ Precis Oncol, 2021, 5(1):69.DOI:10.1038/s41698-021-00206-y.
[11] Xu CW, Si L, Wang WX, et al.Expert consensus on the diagnosis and treatment of NTRK gene fusion solid tumors in China[J].Thorac Cancer, 2022, 13(21):3084-3097.DOI:10.1111/1759-7714.14644.
[12] Amatu A, Sartore-Bianchi A, Siena S.NTRK gene fusions as novel targets of cancer therapy across multiple tumour types[J].ESMO Open, 2016, 1(2):e000023.DOI:10.1136/esmoopen-2015-000023.
[13] Hsiao SJ, Zehir A, Sireci AN, et al.Detection of tumor NTRK gene fusions to identify patients who May benefit from tyrosine kinase (TRK) inhibitor therapy[J].J Mol Diagn, 2019, 21(4):553-571.DOI:10.1016/j.jmoldx.2019.03.008.
[14] Drilon A, Laetsch TW, Kummar S, et al.Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children[J].N Engl J Med, 2018, 378(8):731-739.DOI:10.1056/NEJMoa1714448.
[15] FDA.FDA approves larotrectinib for solid tumors with NTRK gene fusions[EB/OL].(2018-12-14)[2022-09-28].https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions.
[16] Doebele RC, Drilon A, Paz-Ares L, et al.Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours:integrated analysis of three phase 1-2 trials[J].Lancet Oncol, 2020, 21(2):271-282.DOI:10.1016/S1470-2045(19)30691-6.
[17] FDA.FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC[EB/OL].(2019-08-16)[2022-09-28].https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinib-ntrk-solid-tumors-and-ros-1-nsclc.
[18] Laetsch TW, DuBois SG, Mascarenhas L, et al.Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions:phase 1 results from a multicentre, open-label, phase 1/2 study[J].Lancet Oncol, 2018, 19(5):705-714.DOI:10.1016/S1470-2045(18)30119-0.
[19] Munkhdelger J, Shimooka T, Koyama Y, et al.Basaloid squamous cell carcinoma of the uterine cervix:report of a case with molecular analysis[J].Int J Surg Pathol, 2021, 29(7):770-774.DOI:10.1177/1066896921997132.
[20] Carter-Febres M, Schneller N, Fair D, et al.Adjuvant maintenance larotrectinib therapy in 2 children with NTRK fusion-positive high-grade cancers[J].J Pediatr Hematol Oncol, 2021, 43(7):e987-e990.DOI:10.1097/MPH.0000000000001983.
[21] Awada A, Berghmans T, Clement PM, et al.Belgian expert consensus for tumor-agnostic treatment of NTRK gene fusion-driven solid tumors with larotrectinib[J].Crit Rev Oncol Hematol, 2022, 169:103564.DOI:10.1016/j.critrevonc.2021.103564.
[22] Drilon A, Nagasubramanian R, Blake JF, et al.A next-generation TRK kinase inhibitor overcomes acquired resistance to prior TRK kinase inhibition in patients with TRK fusion-positive solid tumors[J].Cancer Discov, 2017, 7(9):963-972.DOI:10.1158/2159-8290.CD-17-0507.
[23] Drilon A, Ou SI, Cho BC, et al.Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent-front mutations[J].Cancer Discov, 2018, 8(10):1227-1236.DOI:10.1158/2159-8290.CD-18-0484.
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备注/Memo
收稿日期:2023-03-06。
通讯作者:吴晔明,Email:wuymsh@163.com