FGFR3-TACC3 fusion proteins act as naturally occurring drivers of tumor resistance by functionally substituting for EGFR/ERK signaling

Oncogene

Volumn 36, Issue 4, 2017, Pages 471-481

  Daly, C ^a   Castanaro, C ^a   Zhang, W ^a   Zhang, Q ^a,b   Wei, Y ^a   Ni, M ^a   Young, T M ^a   Zhang, L ^a   Burova, E ^a   Thurston, G ^a  

^a REGENERON PHARMACEUTICALS INC   (United States)

^b GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 (2,6 DICHLOROBENZYLSULFONYL) 3 [3,5 DIMETHYL 4 [2 (1 PYRROLIDINYLMETHYL) 1 PYRROLIDINYLCARBONYL] 1H PYRROL 2 YLMETHYLENE] 1,3 DIHYDRO 2H INDOL 2 ONE; ALPELISIB; AZD 4547; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 3; FIBROBLAST GROWTH FACTOR RECEPTOR 3; MITOGEN ACTIVATED PROTEIN KINASE; OSIMERTINIB; PROTEIN; TACC3 PROTEIN; TRAMETINIB; UNCLASSIFIED DRUG; ANTIBODY; EGFR PROTEIN, HUMAN; FGFR3 PROTEIN, HUMAN; MICROTUBULE ASSOCIATED PROTEIN; ONCOPROTEIN; TACC3 PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; BLADDER CANCER; CANCER INHIBITION; CANCER PATIENT; CLINICAL ARTICLE; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG MECHANISM; FEMALE; FUSION GENE; GENE OVEREXPRESSION; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; IN VITRO STUDY; LUNG CANCER CELL LINE; MOLECULAR WEIGHT; MOUSE; MULTIPLE CANCER; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; RNA SEQUENCE; SANGER SEQUENCING; TUMOR RESISTANCE; TUMOR VOLUME; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CARCINOMA, SQUAMOUS CELL; DRUG RESISTANCE; DRUG SCREENING; GENETIC TRANSFECTION; GENETICS; HEAD AND NECK NEOPLASMS; IMMUNOLOGY; MAPK SIGNALING; METABOLISM; PATHOLOGY; RANDOMIZATION; SCID MOUSE; TUMOR CELL LINE;

ANIMALS; ANTIBODIES; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; FEMALE; HEAD AND NECK NEOPLASMS; HUMANS; MAP KINASE SIGNALING SYSTEM; MICE; MICE, SCID; MICROTUBULE-ASSOCIATED PROTEINS; ONCOGENE PROTEINS, FUSION; RANDOM ALLOCATION; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 3; TRANSFECTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84976314171     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2016.216     Document Type: Article

References (47)

1. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497-1500.
2. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7: 169-181.
3. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head, neck. N Engl J Med 2006; 354: 567-578.
4. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy, cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337-345.
5. Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007; 357: 2040-2048.
6. Chong CR, Janne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med 2013; 19: 1389-1400.
7. Misale S, Di Nicolantonio F, Sartore-Bianchi A, Siena S, Bardelli A. Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution. Cancer Discov 2014; 4: 1269-1280.
8. Arteaga CL, Engelman JA. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 2014; 25: 282-303.
9. Gala K, Chandarlapaty S. Molecular pathways: HER3 targeted therapy. Clin Cancer Res 2014; 20: 1410-1416.
10. Garner AP, Bialucha CU, Sprague ER, Garrett JT, Sheng Q, Li S, et al. An antibody that locks HER3 in the inactive conformation inhibits tumor growth driven by HER2 or neuregulin. Cancer Res 2013; 73: 6024-6035.
11. Huang S, Li C, Armstrong EA, Peet CR, Saker J, Amler LC, et al. Dual targeting of EGFR, HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors, radiation. Cancer Res 2013; 73: 824-833.
12. Schaefer G, Haber L, Crocker LM, Shia S, Shao L, Dowbenko D, et al. A two-in-one antibody against HER3, EGFR has superior inhibitory activity compared with monospecific antibodies. Cancer Cell 2011; 20: 472-486.
13. Zhang L, Castanaro C, Luan B, Yang K, Fan L, Fairhurst JL, et al. ERBB3/HER2 signaling promotes resistance to EGFR blockade in head, neck, colorectal cancer models. Mol Cancer Ther 2014; 13: 1345-1355.
14. Jiang N, Wang D, Hu Z, Shin HJ, Qian G, Rahman MA, et al. Combination of anti-HER3 antibody MM-121/SAR256212, cetuximab inhibits tumor growth in preclinical models of head, neck squamous cell carcinoma. Mol Cancer Ther 2014; 13: 1826-1836.
15. Engelman JA, Janne PA, Mermel C, Pearlberg J, Mukohara T, Fleet C, et al. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci USA 2005; 102: 3788-3793.
16. Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF 3rd, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci USA 2003; 100: 8933-8938.
17. Soltoff SP, Carraway KL 3rd, Prigent SA, Gullick WG, Cantley LC. ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor. Mol Cell Biol 1994; 14: 3550-3558.
18. LoRusso P, Janne PA, Oliveira M, Rizvi N, Malburg L, Keedy V, et al. Phase I study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res 2013; 19: 3078-3087.
19. Mirschberger C, Schiller CB, Schraml M, Dimoudis N, Friess T, Gerdes CA, et al. RG7116, a therapeutic antibody that binds the inactive HER3 receptor, is optimized for immune effector activation. Cancer Res 2013; 73: 5183-5194.
20. Schoeberl B, Pace EA, Fitzgerald JB, Harms BD, Xu L, Nie L, et al. Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis. Sci Signal 2009; 2: ra31.
21. Knowles M.A. Novel therapeutic targets in bladder cancer: mutation, expression of FGF receptors. Future Oncol 2008; 4: 71-83.
22. Parker BC, Annala MJ, Cogdell DE, Granberg KJ, Sun Y, Ji P, et al. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J Clin Invest 2013; 123: 855-865.
23. Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R, Castano A, et al. Transforming fusions of FGFR, TACC genes in human glioblastoma. Science 2012; 337: 1231-1235.
24. Williams SV, Hurst CD, Knowles M.A. Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Genet 2013; 22: 795-803.
25. Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov 2013; 3: 636-647.
26. Nelson KN, Meyer AN, Siari A, Campos AR, Motamedchaboki K, Donoghue DJ. Oncogenic gene fusion FGFR3-TACC3 is regulated by tyrosine phosphorylation. Mol Cancer Res 2016; 14: 458-469.
27. Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating, targeting genomes. Nat Biotechnol 2014; 32: 347-355.
28. Cancer Genome Atlas Network. Comprehensive genomic characterization of head, neck squamous cell carcinomas. Nature 2015; 517: 576-582.
29. Capelletti M, Dodge ME, Ercan D, Hammerman PS, Park SI, Kim J, et al. Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma. Clin Cancer Res 2014; 20: 6551-6558.
30. Di Stefano AL, Fucci A, Frattini V, Labussiere M, Mokhtari K, Zoppoli P, et al. Detection, characterization, inhibition of FGFR-TACC fusions in IDH wild type glioma. Clin Cancer Res 2015; 21: 3307-3317.
31. Kim Y, Hammerman PS, Kim J, Yoon JA, Lee Y, Sun JM, et al. Integrative, comparative genomic analysis of lung squamous cell carcinomas in East Asian patients. J Clin Oncol 2014; 32: 121-128.
32. Yuan L, Liu ZH, Lin ZR, Xu LH, Zhong Q, Zeng MS. Recurrent FGFR3-TACC3 fusion gene in nasopharyngeal carcinoma. Cancer Biol Ther 2014; 15: 1613-1621.
33. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun 2014; 5: 4846.
34. Wang R, Wang L, Li Y, Hu H, Shen L, Shen X, et al. FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer. Clin Cancer Res 2014; 20: 4107-4114.
35. Lamont FR, Tomlinson DC, Cooper PA, Shnyder SD, Chester JD, Knowles M.A. Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro, in vivo. Br J Cancer 2011; 104: 75-82.
36. Crystal AS, Shaw AT, Sequist LV, Friboulet L, Niederst MJ, Lockerman EL, et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science 2014; 346: 1480-1486.
37. Herrera-Abreu MT, Pearson A, Campbell J, Shnyder SD, Knowles MA, Ashworth A, et al. Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3-mutant cancer. Cancer Discov 2013; 3: 1058-1071.
38. Oliveras-Ferraros C, Cufi S, Queralt B, Vazquez-Martin A, Martin-Castillo B, de Llorens R, et al. Cross-suppression of EGFR ligands amphiregulin, epiregulin, de-repression of FGFR3 signalling contribute to cetuximab resistance in wildtype KRAS tumour cells. Br J Cancer 2012; 106: 1406-1414.
39. Ware KE, Marshall ME, Heasley LR, Marek L, Hinz TK, Hercule P, et al. Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2, FGFR3 expression. PLoS One 2010; 5: e14117.
40. Jebar AH, Hurst CD, Tomlinson DC, Johnston C, Taylor CF, Knowles M.A. FGFR3, Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene 2005; 24: 5218-5225.
41. di Martino E, L'Hote CG, Kennedy W, Tomlinson DC, Knowles M.A. Mutant fibroblast growth factor receptor 3 induces intracellular signaling, cellular transformation in a cell type-, mutation-specific manner. Oncogene 2009; 28: 4306-4316.
42. Juanpere N, Agell L, Lorenzo M, de Muga S, Lopez-Vilaro L, Murillo R, et al. Mutations in FGFR3, PIK3CA, singly or combined with RAS, AKT1, are associated with AKT but not with MAPK pathway activation in urothelial bladder cancer. Hum Pathol 2012; 43: 1573-1582.
43. Helsten T, Elkin S, Arthur E, Tomson BN, Carter J, Kurzrock R. The Fgfr landscape in cancer: analysis of 4853 tumors by next generation sequencing. Clin Cancer Res 2016; 22: 259-267.
44. Gaykalova DA, Mambo E, Choudhary A, Houghton J, Buddavarapu K, Sanford T, et al. Novel insight into mutational landscape of head, neck squamous cell carcinoma. PLoS One 2014; 9: e93102.
45. Marshall ME, Hinz TK, Kono SA, Singleton KR, Bichon B, Ware KE, et al. Fibroblast growth factor receptors are components of autocrine signaling networks in head, neck squamous cell carcinoma cells. Clin Cancer Res 2011; 17: 5016-5025.
46. Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, et al. Integrative, comparative genomic analysis of HPV-positive, HPV-negative head, neck squamous cell carcinomas. Clin Cancer Res 2015; 21: 632-641.
47. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, et al. Genomescale CRISPR-Cas9 knockout screening in human cells. Science 2014; 343: 84-87.