Subscribe to RSS
![](/products/assets/desktop/img/oa-logo.png)
DOI: 10.1055/s-0042-1758542
Hallmarks of Anaplastic Lymphoma Kinase Inhibitors with Its Quick Emergence of Drug Resistance
![](https://www.thieme-connect.de/media/10.1055-s-00043364/202204/lookinside/thumbnails/10-1055-s-0042-1758542_2200012-1.jpg)
Abstract
Anaplastic lymphoma kinase (ALK) is one of the most popular targets for anticancer therapies. In the past decade, the use of anaplastic lymphoma tyrosine kinase inhibitors (ALK-TKIs), including crizotinib and ceritinib, has been a reliable and standard options for patients with lung cancer, particularly for patients with nonsmall cell lung carcinoma. ALK-targeted therapies initially benefit the patients, yet, resistance eventually occurs. Therefore, resistance mechanisms of ALK-TKIs and the solutions have become a formidable challenge in the development of ALK inhibitors. In this review, based on the knowledge of reported ALK inhibitors, we illustrated the crystal structures of ALK, summarized the resistance mechanisms of ALK-targeted drugs, and proposed potential therapeutic strategies to prevent or overcome the resistance.
Publication History
Received: 18 March 2022
Accepted: 30 September 2022
Article published online:
09 December 2022
© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Lovly CM, Pao W. Escaping ALK inhibition: mechanisms of and strategies to overcome resistance. Sci Transl Med 2012; 4 (120): 120ps2
- 2 Shaw AT, Engelman JA. ALK in lung cancer: past, present, and future. J Clin Oncol 2013; 31 (08) 1105-1111
- 3 Choi YL, Soda M, Yamashita Y. et al. ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med 2010; 363 (18) 1734-1739
- 4 Hallberg B, Palmer RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer 2013; 13 (10) 685-700
- 5 Friboulet L, Li N, Katayama R. et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov 2014; 4 (06) 662-673
- 6 Li J, Pithavala YK, Gong J, LaBadie RR, Mfopou JK, Chen J. The effect of modafinil on the safety and pharmacokinetics of lorlatinib: a phase I study in healthy participants. Clin Pharmacokinet 2021; 60 (10) 1303-1312
- 7 Shaw AT, Bauer TM, de Marinis F. et al. CROWN Trial Investigators. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med 2020; 383 (21) 2018-2029
- 8 Morris SW, Kirstein MN, Valentine MB. et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994; 263 (5151): 1281-1284
- 9 Morris SW, Kirstein MN, Valentine MB. et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994; 263 (5151): 1281-1284
- 10 Rodig SJ, Shapiro GI. Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases. Curr Opin Investig Drugs 2010; 11 (12) 1477-1490
- 11 Doebele RC, Pilling AB, Aisner DL. et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 2012; 18 (05) 1472-1482
- 12 Lovly CM, McDonald NT, Chen H. et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med 2014; 20 (09) 1027-1034
- 13 Zhang C, Han XR, Yang X. et al. Proteolysis Targeting Chimeras (PROTACs) of anaplastic lymphoma kinase (ALK). Eur J Med Chem 2018; 151: 304-314
- 14 Roskoski Jr R. Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition. Pharmacol Res 2013; 68 (01) 68-94
- 15 Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov 2017; 16 (02) 101-114
- 16 Wellstein A, Toretsky JA. Hunting ALK to feed targeted cancer therapy. Nat Med 2011; 17 (03) 290-291
- 17 Isozaki H, Takigawa N, Kiura K. Mechanisms of acquired resistance to ALK inhibitors and the rationale for treating ALK-positive lung cancer. Cancers (Basel) 2015; 7 (02) 763-783
- 18 Liu J, Ma S. Recent development in the discovery of anaplastic lymphoma kinase (ALK) inhibitors for non-small cell lung cancer. Curr Med Chem 2017; 24 (06) 590-613
- 19 Chen Y, Takita J, Choi YL. et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature 2008; 455 (7215): 971-974
- 20 Sasaki T, Okuda K, Zheng W. et al. The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res 2010; 70 (24) 10038-10043
- 21 Katayama R, Shaw AT, Khan TM. et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med 2012; 4 (120): 120ra17
- 22 Mehlman C, Chaabane N, Lacave R. et al. Ceritinib ALK T1151R resistance mutation in lung cancer with initial response to brigatinib. J Thorac Oncol 2019; 14 (05) e95-e96
- 23 Pan Y, Deng C, Qiu Z, Cao C, Wu F. The resistance mechanisms and treatment strategies for ALK-rearranged non-small cell lung cancer. Front Oncol 2021; 11: 713530
- 24 Sasaki T, Koivunen J, Ogino A. et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res 2011; 71 (18) 6051-6060
- 25 Basit S, Ashraf Z, Lee K, Latif M. First macrocyclic 3rd-generation ALK inhibitor for treatment of ALK/ROS1 cancer: clinical and designing strategy update of lorlatinib. Eur J Med Chem 2017; 134: 348-356
- 26 Chand D, Yamazaki Y, Ruuth K. et al. Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma. Dis Model Mech 2013; 6 (02) 373-382
- 27 Mossé YP, Laudenslager M, Longo L. et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 2008; 455 (7215): 930-935
- 28 Schönherr C, Ruuth K, Yamazaki Y. et al. Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684. Biochem J 2011; 440 (03) 405-413
- 29 George RE, Sanda T, Hanna M. et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008; 455 (7215): 975-978
- 30 Martinsson T, Eriksson T, Abrahamsson J. et al. Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumor progression and unresponsiveness to therapy. Cancer Res 2011; 71 (01) 98-105
- 31 Carén H, Abel F, Kogner P, Martinsson T. High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochem J 2008; 416 (02) 153-159
- 32 Janoueix-Lerosey I, Lequin D, Brugières L. et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 2008; 455 (7215): 967-970
- 33 Schulte JH, Bachmann HS, Brockmeyer B. et al. High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining factor of an unfavorable phenotype in primary neuroblastoma. Clin Cancer Res 2011; 17 (15) 5082-5092
- 34 Heuckmann JM, Hölzel M, Sos ML. et al. ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin Cancer Res 2011; 17 (23) 7394-7401
- 35 Murugan AK, Xing M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res 2011; 71 (13) 4403-4411
- 36 McDuff FK, Lim SV, Dalbay M, Turner SD. Assessment of the transforming potential of novel anaplastic lymphoma kinase point mutants. Mol Carcinog 2013; 52 (01) 79-83
- 37 Choi HG, Ren P, Adrian F. et al. A type-II kinase inhibitor capable of inhibiting the T315I “gatekeeper” mutant of Bcr-Abl. J Med Chem 2010; 53 (15) 5439-5448
- 38 Guan H, Du Y, Ning Y, Cao X. A brief perspective of drug resistance toward EGFR inhibitors: the crystal structures of EGFRs and their variants. Future Med Chem 2017; 9 (07) 693-704
- 39 Marsilje TH, Pei W, Chen B. et al. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem 2013; 56 (14) 5675-5690
- 40 Wang Y, Zhang G, Hu G. et al. Design, synthesis and biological evaluation of novel 4-arylaminopyrimidine derivatives possessing a hydrazone moiety as dual inhibitors of L1196M ALK and ROS1. Eur J Med Chem 2016; 123: 80-89
- 41 Pan P, Yu H, Liu Q. et al. Combating drug-resistant mutants of anaplastic lymphoma kinase with potent and selective type-I1/2 inhibitors by stabilizing unique DFG-shifted loop conformation. ACS Cent Sci 2017; 3 (11) 1208-1220
- 42 Ni Z, Wang X, Zhang T, Jin RZ. Molecular dynamics simulations reveal the allosteric effect of F1174C resistance mutation to ceritinib in ALK-associated lung cancer. Comput Biol Chem 2016; 65: 54-60
- 43 Bresler SC, Wood AC, Haglund EA. et al. Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Sci Transl Med 2011; 3 (108): 108ra114
- 44 Yang PCR, Bao H, Wu X. et al. Identification of novel alectinib-resistant ALK mutation G1202K with sensitization to lorlatinib: a case report and in silico structural modelling. Onco Targets Ther 2021; 14: 2131-2138
- 45 Tabbò F, Reale ML, Bironzo P, Scagliotti GV. Resistance to anaplastic lymphoma kinase inhibitors: knowing the enemy is half the battle won. Transl Lung Cancer Res 2020; 9 (06) 2545-2556
- 46 Zhu VW, Nagasaka M, Madison R, Schrock AB, Cui J, Ou SI. A novel sequentially evolved EML4-ALK variant 3 G1202R/S1206Y double mutation in Cis confers resistance to lorlatinib: a brief report and literature review. JTO Clin Res Rep 2020; 2 (01) 100116
- 47 Okada K, Araki M, Sakashita T. et al. Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance. EBioMedicine 2019; 41: 105-119
- 48 Baglivo S, Ricciuti B, Ludovini V. et al. Dramatic response to lorlatinib in a heavily pretreated lung adenocarcinoma patient harboring G1202R mutation and a synchronous novel R1192P ALK point mutation. J Thorac Oncol 2018; 13 (08) e145-e147
- 49 Wang Z, Geng Y, Yuan LY. et al. Durable clinical response to ALK tyrosine kinase inhibitors in epithelioid inflammatory myofibroblastic sarcoma harboring PRRC2B-ALK rearrangement: a case report. Front Oncol 2022; 12: 761558
- 50 Heregger R, Huemer F, Hutarew G. et al. Sustained response to brigatinib in a patient with refractory metastatic pheochromocytoma harboring R1192P anaplastic lymphoma kinase mutation: a case report from the Austrian Group Medical Tumor Therapy next-generation sequencing registry and discussion of the literature. ESMO Open 2021; 6 (04) 100233
- 51 Kobayashi T, Kanda S, Fukushima T, Noguchi T, Sekiguchi N, Koizumi T. Response to lorlatinib on a patient with ALK-rearranged non-small cell lung cancer harboring 1151Tins mutation with uterine metastasis. Thorac Cancer 2021; 12 (16) 2275-2278
- 52 Furuta H, Araki M, Masago K. et al. Novel resistance mechanisms including L1196Q, P1094H, and R1248_D1249 insertion in three patients with NSCLC after ALK tyrosine kinase inhibitor treatment. J Thorac Oncol 2021; 16 (03) 477-482
- 53 Yao S, Cheng M, Zhang Q, Wasik M, Kelsh R, Winkler C. Anaplastic lymphoma kinase is required for neurogenesis in the developing central nervous system of zebrafish. PLoS One 2013; 8 (05) e63757
- 54 Soda M, Choi YL, Enomoto M. et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448 (7153): 561-566
- 55 Katayama R, Khan TM, Benes C. et al. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A 2011; 108 (18) 7535-7540
- 56 Zhang SS, Nagasaka M, Zhu VW, Ou SI. Going beneath the tip of the iceberg. Identifying and understanding EML4-ALK variants and TP53 mutations to optimize treatment of ALK fusion positive (ALK+) NSCLC. Lung Cancer 2021; 158: 126-136
- 57 Horn L, Whisenant JG, Wakelee H. et al. Monitoring therapeutic response and resistance: analysis of circulating tumor DNA in patients with ALK+ lung cancer. J Thorac Oncol 2019; 14 (11) 1901-1911
- 58 Tulpule A, Guan J, Neel DS. et al. Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules. Cell 2021; 184 (10) 2649-2664.e18
- 59 Tanimoto A, Matsumoto S, Takeuchi S. et al. Proteasome inhibition overcomes ALK-TKI resistance in ALK-rearranged/TP53-mutant NSCLC via noxa expression. Clin Cancer Res 2021; 27 (05) 1410-1420
- 60 Cools J, Wlodarska I, Somers R. et al. Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2002; 34 (04) 354-362
- 61 Hernández L, Beà S, Bellosillo B. et al. Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity. Am J Pathol 2002; 160 (04) 1487-1494
- 62 Hernández L, Pinyol M, Hernández S. et al. TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations. Blood 1999; 94 (09) 3265-3268
- 63 Tort F, Pinyol M, Pulford K. et al. Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma. Lab Invest 2001; 81 (03) 419-426
- 64 Tort F, Campo E, Pohlman B, Hsi E. Heterogeneity of genomic breakpoints in MSN-ALK translocations in anaplastic large cell lymphoma. Hum Pathol 2004; 35 (08) 1038-1041
- 65 Lamant L, Dastugue N, Pulford K, Delsol G, Mariamé B. A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Blood 1999; 93 (09) 3088-3095
- 66 Siebert R, Gesk S, Harder L. et al. Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma. Blood 1999; 94 (10) 3614-3617
- 67 Meech SJ, McGavran L, Odom LF. et al. Unusual childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4–anaplastic lymphoma kinase gene fusion. Blood 2001; 98 (04) 1209-1216
- 68 Ma Z, Cools J, Marynen P. et al. Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive anaplastic lymphoma kinase (ALK) tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis. Blood 2000; 95 (06) 2144-2149
- 69 Colleoni GW, Bridge JA, Garicochea B, Liu J, Filippa DA, Ladanyi M. ATIC-ALK: a novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35). Am J Pathol 2000; 156 (03) 781-789
- 70 Trinei M, Lanfrancone L, Campo E. et al. A new variant anaplastic lymphoma kinase (ALK)-fusion protein (ATIC-ALK) in a case of ALK-positive anaplastic large cell lymphoma. Cancer Res 2000; 60 (04) 793-798
- 71 Lamant L, Gascoyne RD, Duplantier MM. et al. Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma. Genes Chromosomes Cancer 2003; 37 (04) 427-432
- 72 Touriol C, Greenland C, Lamant L. et al. Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like). Blood 2000; 95 (10) 3204-3207
- 73 Rikova K, Guo A, Zeng Q. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007; 131 (06) 1190-1203
- 74 Masood A, Christ T, Asif S. et al. Non-secretory multiple myeloma with unusual TFG-ALK fusion showed dramatic response to ALK inhibition. NPJ Genom Med 2021; 6 (01) 23
- 75 Takeuchi K, Choi YL, Togashi Y. et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 2009; 15 (09) 3143-3149
- 76 Wong DW, Leung EL, Wong SK. et al. A novel KIF5B-ALK variant in nonsmall cell lung cancer. Cancer 2011; 117 (12) 2709-2718
- 77 Togashi Y, Soda M, Sakata S. et al. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS One 2012; 7 (02) e31323
- 78 Jung Y, Kim P, Jung Y. et al. Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing. Genes Chromosomes Cancer 2012; 51 (06) 590-597
- 79 Lawrence B, Perez-Atayde A, Hibbard MK. et al. TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am J Pathol 2000; 157 (02) 377-384
- 80 Bridge JA, Kanamori M, Ma Z. et al. Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. Am J Pathol 2001; 159 (02) 411-415
- 81 Patel AS, Murphy KM, Hawkins AL. et al. RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors. Cancer Genet Cytogenet 2007; 176 (02) 107-114
- 82 Debiec-Rychter M, Marynen P, Hagemeijer A, Pauwels P. ALK-ATIC fusion in urinary bladder inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2003; 38 (02) 187-190
- 83 Debelenko LV, Arthur DC, Pack SD, Helman LJ, Schrump DS, Tsokos M. Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor. Lab Invest 2003; 83 (09) 1255-1265
- 84 Mariño-Enríquez A, Wang WL, Roy A. et al. Epithelioid inflammatory myofibroblastic sarcoma: An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol 2011; 35 (01) 135-144
- 85 Panagopoulos I, Nilsson T, Domanski HA. et al. Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor. Int J Cancer 2006; 118 (05) 1181-1186
- 86 Onciu M, Behm FG, Downing JR. et al. ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases. Blood 2003; 102 (07) 2642-2644
- 87 Adam P, Katzenberger T, Seeberger H. et al. A case of a diffuse large B-cell lymphoma of plasmablastic type associated with the t(2;5)(p23;q35) chromosome translocation. Am J Surg Pathol 2003; 27 (11) 1473-1476
- 88 De Paepe P, Baens M, van Krieken H. et al. ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma. Blood 2003; 102 (07) 2638-2641
- 89 Takeuchi K, Soda M, Togashi Y. et al. Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma. Haematologica 2011; 96 (03) 464-467
- 90 Van Roosbroeck K, Cools J, Dierickx D. et al. ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions. Haematologica 2010; 95 (03) 509-513
- 91 Lin E, Li L, Guan Y. et al. Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol Cancer Res 2009; 7 (09) 1466-1476
- 92 Lipson D, Capelletti M, Yelensky R. et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 2012; 18 (03) 382-384
- 93 Jazii FR, Najafi Z, Malekzadeh R. et al. Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer. World J Gastroenterol 2006; 12 (44) 7104-7112
- 94 Du XL, Hu H, Lin DC. et al. Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma. J Mol Med (Berl) 2007; 85 (08) 863-875
- 95 Debelenko LV, Raimondi SC, Daw N. et al. Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum. Mod Pathol 2011; 24 (03) 430-442
- 96 Fang DD, Zhang B, Gu Q. et al. HIP1-ALK, a novel ALK fusion variant that responds to crizotinib. J Thorac Oncol 2014; 9 (03) 285-294
- 97 Kim RN, Choi YL, Lee MS. et al. SEC31A-ALK fusion gene in lung adenocarcinoma. Cancer Res Treat 2016; 48 (01) 398-402
- 98 Zhang M, Wang Q, Ding Y. et al. CUX1-ALK, a novel ALK rearrangement that responds to crizotinib in non-small cell lung cancer. J Thorac Oncol 2018; 13 (11) 1792-1797
- 99 Zhu VW, Schrock AB, Bosemani T, Benn BS, Ali SM, Ou SI. Dramatic response to alectinib in a lung cancer patient with a novel VKORC1L1-ALK fusion and an acquired ALK T1151K mutation. Lung Cancer (Auckl) 2018; 9: 111-116
- 100 Yin J, Zhang Y, Zhang Y, Peng F, Lu Y. Reporting on two novel fusions, DYSF-ALK and ITGAV-ALK, coexisting in one patient with adenocarcinoma of lung, sensitive to crizotinib. J Thorac Oncol 2018; 13 (03) e43-e45
- 101 Feng T, Chen Z, Gu J, Wang Y, Zhang J, Min L. The clinical responses of TNIP2-ALK fusion variants to crizotinib in ALK-rearranged lung adenocarcinoma. Lung Cancer 2019; 137: 19-22
- 102 Zhou X, Shou J, Sheng J. et al. Molecular and clinical analysis of Chinese patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer. Cancer Sci 2019; 110 (10) 3382-3390
- 103 Tian P, Liu Y, Zeng H. et al. Unique molecular features and clinical outcomes in young patients with non-small cell lung cancer harboring ALK fusion genes. J Cancer Res Clin Oncol 2020; 146 (04) 935-944
- 104 Li Z, Li P, Yan B. et al. Sequential ALK inhibitor treatment benefits patient with leptomeningeal metastasis harboring non-EML4-ALK rearrangements detected from cerebrospinal fluid: a case report. Thorac Cancer 2020; 11 (01) 176-180
- 105 Qiu L, Weitzman SP, Nastoupil LJ, Williams MD, Medeiros LJ, Vega F. Disseminated ALK-positive histiocytosis with KIF5B-ALK fusion in an adult. Leuk Lymphoma 2021; 62 (05) 1234-1238
- 106 Liu W, Duan Q, Gong L. et al. A novel LRRFIP1-ALK fusion in inflammatory myofibroblastic tumor of hip and response to crizotinib. Invest New Drugs 2021; 39 (01) 278-282
- 107 Zhong Y, Lin F, Xu F. et al. Genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma. Cancer Genet 2021; 252–253: 37-42
- 108 Crystal AS, Shaw AT, Sequist LV. et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science 2014; 346 (6216): 1480-1486
- 109 Wu YL, Soo RA, Locatelli G, Stammberger U, Scagliotti G, Park K. Does c-Met remain a rational target for therapy in patients with EGFR TKI-resistant non-small cell lung cancer?. Cancer Treat Rev 2017; 61: 70-81
- 110 Jordana-Ariza N, Reischmann N, Esparré C. et al. Abstract 1106: detection of MET alterations at the DNA, RNA and protein levels in NSCLC patients progressing on ALK and ROS1 targeted therapies. Cancer Res 2022; 82 (12, Supplement): 1106
- 111 Sakakibara-Konishi J, Kitai H, Ikezawa Y. et al. Response to crizotinib re-administration after progression on lorlatinib in a patient with ALK-rearranged non-small-cell lung cancer. Clin Lung Cancer 2019; 20 (05) e555-e559
- 112 Dagogo-Jack I, Yoda S, Lennerz JK. et al. MET alterations are a recurring and actionable resistance mechanism in ALK-positive lung cancer. Clin Cancer Res 2020; 26 (11) 2535-2545
- 113 Karaca Atabay E, Mecca C, Wang Q. et al. Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma. Blood 2022; 139 (05) 717-731
- 114 Lang GT, Jiang YZ, Shi JX. et al. Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing. Nat Commun 2020; 11 (01) 5679
- 115 Recondo G, Mezquita L, Facchinetti F. et al. Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. Clin Cancer Res 2020; 26 (01) 242-255
- 116 Cui JJ, Rogers E, Zhai D. et al. Abstract 5226: TPX-0131: a next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors. Cancer Res 2020; 80 (16, Supplement): 5226
- 117 Murray BW, Zhai D, Deng W. et al. TPX-0131, a Potent CNS-penetrant, next-generation inhibitor of wild-type ALK and ALK-resistant mutations. Mol Cancer Ther 2021; 20 (09) 1499-1507
- 118 Sun X, Gao H, Yang Y. et al. PROTACs: great opportunities for academia and industry. Signal Transduct Target Ther 2019; 4: 64
- 119 Sun N, Ren C, Kong Y. et al. Development of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance. Eur J Med Chem 2020; 193: 112190
- 120 Ren C, Sun N, Kong Y. et al. Structure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib. Eur J Med Chem 2021; 217: 113335