Dovitinib (TKI258), a multi-target angiokinase inhibitor, is effective regardless of KRAS or BRAF mutation status in colorectal cancer

American Journal of Cancer Research

Volumn 5, Issue 1, 2015, Pages 72-86

  Lee, Choong Kun ^a   Lee, Myung Eun ^b   Lee, Won Suk ^b   Kim, Jeong Min ^b   Park, Kyu Hyun ^b   Kim, Tae Soo ^b   Lee, Kang Young ^c   Ahn, Joong Bae ^a,b   Chung, Hyun Cheol ^a,b   Rha, Sun Young ^a,b  

^a Yonsei University College of Medicine   (South Korea)

^b Yonsei University College of Medicine   (South Korea)

^c Yonsei University College of Medicine   (South Korea)

Author keywords

BRAF; Colorectal cancer; Dovitinib (TKI258); FGFR; KRAS; Multi target angiokinase inhibitor

Indexed keywords

B RAF KINASE; CD31 ANTIGEN; DOVITINIB; FIBROBLAST GROWTH FACTOR RECEPTOR 1; FIBROBLAST GROWTH FACTOR RECEPTOR 3; K RAS PROTEIN; KI 67 ANTIGEN; P70S6K KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN SERINE THREONINE KINASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BRAF GENE; CANCER INHIBITION; CLINICAL EFFECTIVENESS; COLORECTAL CANCER; COLORECTAL CANCER CELL LINE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG DETERMINATION; DRUG SCREENING; DRUG SENSITIVITY; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; GENE MUTATION; GENETIC VARIABILITY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NICK END LABELING; NONHUMAN; ONCOGENE; ONCOGENE K RAS; PROTEIN TARGETING; SIGNAL TRANSDUCTION; TUMOR VOLUME; TUMOR XENOGRAFT;

EID: 84968839745     PISSN: None     EISSN: 21566976     Source Type: Journal    
DOI: None     Document Type: Article

References (50)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90.
2. Center MM, Jemal A and Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev 2009; 18: 1688-1694.
3. Shaheen RM, Davis DW, Liu W, Zebrowski BK, Wilson MR, Bucana CD, McConkey DJ, McMahon G and Ellis LM. Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res 1999; 59: 5412-5416.
4. Shaheen RM, Tseng WW, Davis DW, Liu W, Reinmuth N, Vellagas R, Wieczorek AA, Ogura Y, McConkey DJ, Drazan KE, Bucana CD, McMahon G and Ellis LM. Tyrosine kinase inhibition of multiple angiogenic growth factor receptors improves survival in mice bearing colon cancer liver metastases by inhibition of endothelial cell survival mechanisms. Cancer Res 2001; 61: 1464-1468.
5. Laird AD and Cherrington JM. Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Expert Opin Investig Drugs 2003; 12: 51-64.
6. McCarthy M. Antiangiogenesis drug promising for metastatic colorectal cancer. Lancet 2003; 361: 1959.
7. Ortega J, Vigil CE and Chodkiewicz C. Current progress in targeted therapy for colorectal cancer. Cancer Control 2010; 17: 7-15.
8. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY and Jain RK. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004; 10: 145-147.
9. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M and Amado RG. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007; 25: 1658-1664.
10. Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J and Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408-1417.
11. Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C and Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007; 357: 2040-2048.
12. Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kroning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J and Burris HA 3rd. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 2311-2319.
13. Sato T, Oshima T, Yoshihara K, Yamamoto N, Yamada R, Nagano Y, Fujii S, Kunisaki C, Shiozawa M, Akaike M, Rino Y, Tanaka K, Masuda M and Imada T. Overexpression of the fibroblast growth factor receptor-1 gene correlates with liver metastasis in colorectal cancer. Oncol Rep 2009; 21: 211-216.
14. Itoh N and Ornitz DM. Evolution of the Fgf and Fgfr gene families. Trends Genet 2004; 20: 563-569.
15. Sonvilla G, Allerstorfer S, Heinzle C, Stattner S, Karner J, Klimpfinger M, Wrba F, Fischer H, Gauglhofer C, Spiegl-Kreinecker S, Grasl-Kraupp B, Holzmann K, Grusch M, Berger W and Marian B. Fibroblast growth factor receptor 3-IIIc mediates colorectal cancer growth and migration. Br J Cancer 2010; 102: 1145-1156.
16. Henriksson ML, Edin S, Dahlin AM, Oldenborg PA, Oberg A, Van Guelpen B, Rutegard J, Stenling R and Palmqvist R. Colorectal cancer cells activate adjacent fibroblasts resulting in FGF1/FGFR3 signaling and increased invasion. Am J Pathol 2011; 178: 1387-1394.
17. Kono SA, Marshall ME, Ware KE and Heasley LE. The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer. Drug Resist Updat 2009; 12: 95-102.
18. Renhowe PA, Pecchi S, Shafer CM, Machajewski TD, Jazan EM, Taylor C, Antonios-McCrea W, McBride CM, Frazier K, Wiesmann M, Lapointe GR, Feucht PH, Warne RL, Heise CC, Menezes D, Aardalen K, Ye H, He M, Le V, Vora J, Jansen JM, Wernette-Hammond ME and Harris AL. Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors. J Med Chem 2009; 52: 278-292.
19. Bardelli A and Siena S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 2010; 28: 1254-1261.
20. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW and Velculescu VE. The consensus coding sequences of human breast and colorectal cancers. Science 2006; 314: 268-274.
21. Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE and Vogelstein B. The genomic landscapes of human breast and colorectal cancers. Science 2007; 318: 1108-1113.
22. Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S and Bardelli A. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 2008; 26: 5705-5712.
23. De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M and Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010; 11: 753-762.
24. Lee J, Lee I, Han B, Park JO, Jang J, Park C and Kang WK. Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations. J Natl Cancer Inst 2011; 103: 674-688.
25. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR and Futreal PA. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949-954.
26. Haigis KM, Kendall KR, Wang Y, Cheung A, Haigis MC, Glickman JN, Niwa-Kawakita M, Sweet-Cordero A, Sebolt-Leopold J, Shannon KM, Settleman J, Giovannini M and Jacks T. Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon. Nat Genet 2008; 40: 600-608.
27. Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F and Laurent-Puig P. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008; 26: 374-379.
28. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 2002; 418: 934.
29. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A and Rettig WJ. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 2008; 68: 4774-4782.
30. Yeh JJ, Routh ED, Rubinas T, Peacock J, Martin TD, Shen XJ, Sandler RS, Kim HJ, Keku TO and Der CJ. KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer. Mol Cancer Ther 2009; 8: 834-843.
31. Oliveira C, Pinto M, Duval A, Brennetot C, Domingo E, Espin E, Armengol M, Yamamoto H, Hamelin R, Seruca R and Schwartz S Jr. BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency. Oncogene 2003; 22: 9192-9196.
32. Squires M, Ward G, Saxty G, Berdini V, Cleasby A, King P, Angibaud P, Perera T, Fazal L, Ross D, Jones CG, Madin A, Benning RK, Vickerstaffe E, O'Brien A, Frederickson M, Reader M, Hamlett C, Batey MA, Rich S, Carr M, Miller D, Feltell R, Thiru A, Bethell S, Devine LA, Graham BL, Pike A, Cosme J, Lewis EJ, Freyne E, Lyons J, Irving J, Murray C, Newell DR and Thompson NT. Potent, selective inhibitors of fibroblast growth factor receptor define fibroblast growth factor dependence in preclinical cancer models. Mol Cancer Ther 2011; 10: 1542-1552.
33. Lee SH, Lopes de Menezes D, Vora J, Harris A, Ye H, Nordahl L, Garrett E, Samara E, Aukerman SL, Gelb AB and Heise C. In vivo target modulation and biological activity of CHIR-258, a multitargeted growth factor receptor kinase inhibitor, in colon cancer models. Clin Cancer Res 2005; 11: 3633-3641.
34. Oricchio E and Wendel HG. Functional genomics lead to new therapies in follicular lymphoma. Ann N Y Acad Sci 2013; 1293: 18-24.
35. Herath NI, Spanevello MD, Doecke JD, Smith FM, Pouponnot C and Boyd AW. Complex expression patterns of Eph receptor tyrosine kinases and their ephrin ligands in colorectal carcinogenesis. Eur J Cancer 2012; 48: 753-762.
36. Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schottle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansen S, Rauh D, Baessmann I, Altmuller J, Wainer Z, Conron M, Wright G, Russell P, Solomon B, Brambilla E, Brambilla C, Lorimier P, Sollberg S, Brustugun OT, Engel-Riedel W, Ludwig C, Petersen I, Sanger J, Clement J, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Cappuzzo F, Ligorio C, Damiani S, Hallek M, Beroukhim R, Pao W, Klebl B, Baumann M, Buettner R, Ernestus K, Stoelben E, Wolf J, Nurnberg P, Perner S and Thomas RK. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010; 2: 62ra93.
37. Billerey C, Chopin D, Aubriot-Lorton MH, Ricol D, Gil Diez de Medina S, Van Rhijn B, Bralet MP, Lefrere-Belda MA, Lahaye JB, Abbou CC, Bonaventure J, Zafrani ES, van der Kwast T, Thiery JP and Radvanyi F. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol 2001; 158: 1955-1959.
38. Jang JH, Shin KH and Park JG. Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers. Cancer Res 2001; 61: 3541-3543.
39. Matsuda Y, Hagio M, Seya T and Ishiwata T. Fibroblast growth factor receptor 2 IIIc as a therapeutic target for colorectal cancer cells. Mol Cancer Ther 2012; 11: 2010-2020.
40. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S and Bardelli A. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 2007; 67: 2643-2648.
41. Laurent-Puig P, Lievre A and Blons H. Mutations and response to epidermal growth factor receptor inhibitors. Clin Cancer Res 2009; 15: 1133-1139.
42. Repasky GA, Chenette EJ and Der CJ. Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis? Trends Cell Biol 2004; 14: 639-647.
43. Hao H, Muniz-Medina VM, Mehta H, Thomas NE, Khazak V, Der CJ and Shields JM. Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Mol Cancer Ther 2007; 6: 2220-2229.
44. Coffee EM, Faber AC, Roper J, Sinnamon MJ, Goel G, Keung L, Wang WV, Vecchione L, de Vriendt V, Weinstein BJ, Bronson RT, Tejpar S, Xavier RJ, Engelman JA, Martin ES and Hung KE. Concomitant BRAF and PI3K/mTOR Blockade Is Required for Effective Treatment of BRAFV600E Colorectal Cancer. Clin Cancer Res 2013; 19: 2688-2698.
45. Feng S, Shao L, Yu W, Gavine P and Ittmann M. Targeting Fibroblast Growth Factor Receptor Signaling Inhibits Prostate Cancer Progression. Clin Cancer Res 2012; 18: 3880-8.
46. Sweeny L, Liu Z, Lancaster W, Hart J, Hartman YE and Rosenthal EL. Inhibition of fibroblasts reduced head and neck cancer growth by targeting fibroblast growth factor receptor. Laryngoscope 2012; 122: 1539-1544.
47. Ellis LM. Angiogenesis and its role in colorectal tumor and metastasis formation. Semin Oncol 2004; 31: 3-9.
48. Turner N and Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 2010; 10: 116-129.
49. Saylor PJ, Escudier B and Michaelson MD. Importance of fibroblast growth factor receptor in neovascularization and tumor escape from antiangiogenic therapy. Clin Genitourin Cancer 2012; 10: 77-83.
50. Wild R, Fager K, Flefleh C, Kan D, Inigo I, Castaneda S, Luo F, Camuso A, McGlinchey K and Rose W. Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels. Mol Cancer Ther 2006; 5: 104-113.