Polypharmacological Kinase Inhibitors: New Hopes for Cancer Therapy

Polypharmacology in Drug Discovery

Volumn , Issue , 2012, Pages 149-165

  Petrelli, Annalisa ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

Clinical oncology; Polypharmacological kinase inhibitors, TKIs; Targeted therapies, RTKs, in cancer therapy

Indexed keywords

EID: 84886024473     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781118098141.ch8     Document Type: Chapter

References (80)

1. Hunter, T. (2000), Signaling-2000 and beyond, Cell 100, 113-127.
2. Baselga, J.; Arribas, J. (2004), Treating cancer's kinase "addiction," Nature Med. 10, 786-787.
3. Carmeliet, P. (2005), VEGF as a key mediator of angiogenesis in cancer, Oncology 69 (Suppl. 3), 4-10.
4. Abramsson, A.; Lindblom, P.; Betsholtz, C. (2003), Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors, J. Clin. Invest. 112, 1142-1151.
5. Moon, S. E.; Dame, M. K.; Remick, D. R.; Elder, J. T.; Varani, J. (2001), Induction of matrix metalloproteinase-1 (MMP-1) during epidermal invasion of the stroma in human skin organ culture:Keratinocyte stimulation of fibroblast MMP-1 production, Br. J Cancer 85, 1600-1605.
6. Weinstein, I. B. (2002), Cancer. Addiction to oncogenes-the Achilles heal of cancer, Science 297, 63-64.
7. Nencioni, A.; Sandy, P.; Dillon, C.; Kissler, S.; Blume-Jensen, P.; et al. (2004), RNA interference for the identification of disease-associated genes, Curr. Opin. Mol. Ther. 6, 136-140.
8. Colomer, R.; Lupu, R.; Bacus, S. S.; Gelmann, E. P. (1994), erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification, Br. J. Cancer 70, 819-825.
9. Aoki, K.; Yoshida, T.; Matsumoto, N.; Ide, H.; Sugimura, T.; et al. (1997), Suppression of Ki-ras p21 levels leading to growth inhibition of pancreatic cancer cell lines with Ki-ras mutation but not those without Ki-ras mutation, Mol. Carcinog., 20, 251-258.
10. Verma, U. N.; Surabhi, R. M.; Schmaltieg, A.; Becerra, C.; Gaynor, R. B. (2003), Small interfering RNAs directed against beta-catenin inhibit the in vitro and in vivo growth of colon cancer cells, Clin. Cancer Res., 9. 1291-1300.
11. Sharma, A.; Trivedi, N. R.; Zimmerman, M. A.; Tuveson, D. A.; Smith, C. D.; et al. (2005), Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors, Cancer Res. 65, 2412-2421.
12. Weinstein, I. B.; Joe, A. K. (2006), Mechanisms of disease: Oncogene addiction-a rationale for molecular targeting in cancer therapy, Nature Clin. Pract. Oncol. 3, 448-457.
13. Weisberg, E.; Manley, P. W.; Cowan-Jacob, S. W.; Hochhaus, A.; Griffin, J. D. (2007), Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia, Nature Rev. Cancer 7, 345-356.
14. Pendergast, A. M.; Quilliam, L. A.; Cripe, L. D.; Bassing, C. H.; Dai, Z.; et al. (1993), BCRABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein, Cell 75, 175-185.
15. Sattler, M.; Salgia, R.; Okuda, K.; Uemura, N.; Durstin, M. A.; et al. (1996), The protooncogene product p120CBL and the adaptor proteins CRKL and c-CRK link c-ABL, p190BCR/ABL and p210BCR/ABL to the phosphatidylinositol-3' kinase pathway, Oncogene 12, 839-846.
16. Duensing, A.; Medeiros, F.; McConarty, B.; Joseph, N. E.; Panigrahy, D.; et al. (2004), Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs), Oncogene 23, 3999-4006.
17. Burger, H.; den Bakker, M. A.; Kros, J. M.; van, T. H.; de Bruin, A. M.; et al. (2005), Activating mutations in c-KIT and PDGFRalpha are exclusively found in gastrointestinal stromal tumors and not in other tumors overexpressing these imatinib mesylate target genes, Cancer Biol. Ther. 4, 1270-1274.
18. Lynch, T. J.; Bell, D.W.; Sordella, R.; Gurubhagavatula, S.; Okimoto, R. A.; et al. (2004), Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib, New Engl. J. Med. 350, 2129-2139.
19. Rubin, B. P.; Duensing, A. (2006), Mechanisms of resistance to small molecule kinase inhibition in the treatment of solid tumors, Lab. Invest. 86, 981-986.
20. Pao, W. (2006), Defining clinically relevant molecular subsets of lung cancer, Cancer Chemother. Pharmacol. 58(Suppl 1), s11-s15.
21. Quintas-Cardama, A.; Kantarjian, H. M.; Cortes, J. E. (2009), Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia, Cancer Control 16, 122-131.
22. Bianco, R.; Shin, I.; Ritter, C. A.; Yakes, F. M.; Basso, A.; et al. (2003), Loss of PTEN/ MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors, Oncogene, 22, 2812-2822.
23. Morgillo, F.; Kim,W. Y.; Kim, E. S.; Ciardiello, F.; Hong,W. K.; et al. (2007), Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib, Clin. Cancer Res. 13, 2795-2803.
24. Engelman, J. A.; Zejnullahu, K.; Mitsudomi, T.; Song, Y.; Hyland, C.; et al. (2007), MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling, Science, 316, 1039-1043.
25. Christensen, J. G.; Schreck, R. E.; Chan, E.;Wang, X.;Yang, C.; et al. (2001), High levels of HER-2 expression alter the ability of epidermal growth factor receptor (EGFR) family tyrosine kinase inhibitors to inhibit EGFR phosphorylation in vivo, Clin. Cancer Res. 7, 4230-4238.
26. Morphy, R. (2010), Selectively nonselective kinase inhibition: Striking the right balance, J. Med. Chem. 53, 1413-1437.
27. Bergers, G.; Benjamin, L. E. (2003), Tumorigenesis and the angiogenic switch, Nature Rev. Cancer 3, 401-410.
28. Bhowmick, N. A.; Neilson, E. G.; Moses, H. L. (2004), Stromal fibroblasts in cancer initiation and progression, Nature 432, 332-337.
29. Cheng, N.; Bhowmick, N. A.; Chytil, A.; Gorksa, A. E.; Brown, K. A.; et al. (2005), Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP-and HGF-mediated signaling networks, Oncogene 24, 5053-5068.
30. Campbell, J. S.; Johnson, M. M.; Bauer, R. L.; Hudkins, K. L.; Gilbertson, D. G.; et al. (2007), Targeting stromal cells for the treatment of platelet-derived growth factor C-induced hepatocellular carcinogenesis, Differentiation 75, 843-852.
31. Bhowmick, N. A.; Chytil, A.; Plieth, D.; Gorska, A. E.; Dumont, N.; et al. (2004), TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia, Science, 303, 848-851.
32. Pietras, K.; Pahler, J.; Bergers, G.; Hanahan, D. (2008), Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting, PLoS. Med. 5, e19.
33. Olumi, A. F.; Grossfeld, G. D.; Hayward, S. W.; Carroll, P. R.; Tlsty, T. D.; et al. (1999), Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium, Cancer Res. 59, 5002-5011.
34. Lynch, C. C.; Matrisian, L. M. (2002), Matrix metalloproteinases in tumor-host cell communication, Differentiation 70, 561-573.
35. Henry, L. R.; Lee, H. O.; Lee, J. S.; Klein-Szanto, A.; Watts, P.; et al. (2007), Clinical implications of fibroblast activation protein in patients with colon cancer, Clin. Cancer Res. 13, 1736-1741.
36. Pagano, J. S.; Blaser, M.; Buendia, M. A.; Damania, B.; Khalili, K.; et al. (2004), Infectious agents and cancer: Criteria for a causal relation, Semin. Cancer Biol., 14, 453-471.
37. Balkwill, F.; Charles, K. A.; Mantovani, A. (2005), Smoldering and polarized inflammation in the initiation and promotion of malignant disease, Cancer Cell 7, 211-217.
38. Leek, R. D.; Lewis, C. E.; Whitehouse, R.; Greenall, M.; Clarke, J.; et al. (1996), Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma, Cancer Res., 56, 4625-4629.
39. Imada, A.; Shijubo, N.; Kojima, H.; Abe, S. (2000), Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma, Eur. Respir. J, 15, 1087-1093.
40. Ribatti, D.; Ennas, M. G.; Vacca, A.; Ferreli, F.; Nico, B.; et al. (2003), Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma, Eur. J. Clin. Invest, 33, 420-425.
41. Goswami, S.; Sahai, E.;Wyckoff, J. B.; Cammer, M.; Cox, D.; et al. (2005), Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop, Cancer Res., 65, 5278-5283.
42. Wyckoff, J. B.; Wang, Y.; Lin, E. Y.; Li, J. F.; Goswami, S.; et al. (2007), Direct visualization of macrophage-assisted tumor, cell intravasation in mammary tumors, Cancer Res., 67, 2649-2656.
43. Coussens, L. M.; Tinkle, C. L.; Hanahan, D.; Werb, Z. (2000), MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis, Cell 103, 481-490.
44. Owen, J. L.; Iragavarapu-Charyulu, V.; Gunja-Smith, Z.; Herbert, L. M.; Grosso, J. F.; et al. (2003), Up-regulation of matrix metalloproteinase-9 in T lymphocytes of mammary tumor bearers: Role of vascular endothelial growth factor, J. Immunol. 171, 4340-4351.
45. Nozawa, H.; Chiu, C.; Hanahan, D. (2006), Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis, Proc. Natl. Acad. Sci. USA 103, 12493-12498.
46. Wyckoff, J.; Wang, W.; Lin, E. Y.; Wang, Y.; Pixley, F.; et al. (2004), A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors, Cancer Res. 64, 7022-7029.
47. Shih, T.; Lindley, C. (2006), Bevacizumab: An angiogenesis inhibitor for the treatment of solid malignancies, Clin. Ther. 28, 1779-1802.
48. Willett, C. G.; Boucher, Y.; Di Tomaso, E.; Duda, D. G.; Munn, L. L.; et al. (2004), Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer, Nature Med. 10, 145-147.
49. Lengauer, C.; Kinzler,K.W.;Vogelstein, B. (1998), Genetic instabilities in human cancers, Nature, 396, 643-649.
50. Motzer, R. J.; Michaelson, M. D.; Redman, B. G.; Hudes, G. R.;Wilding, G.; et al. (2006), Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma, J. Clin. Oncol. 24, 16-24.
51. Motzer, R. J.; Hoosen, S.; Bello, C. L.; Christensen, J. G. (2006), Sunitinib malate for the treatment of solid tumours: A review of current clinical data, Expert Opin. Invest. Drugs 15, 553-561.
52. Burstein, H. J.; Elias, A. D.; Rugo, H. S.; Cobleigh, M. A.;Wolff, A. C.; et al. (2008), Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J. Clin. Oncol, 26, 1810-1816.
53. Potapova, O.; Laird, A. D.; Nannini, M. A.; Barone, A.; Li, G.; et al. (2006), Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248, Mol. Cancer Ther. 5, 1280-1289.
54. Faivre, S.; Demetri, G.; Sargent, W.; Raymond, E. (2007), Molecular basis for sunitinib efficacy and future clinical development, Nature Rev. Drug Discov. 6, 734-745.
55. O'Farrell, A. M.; Abrams, T. J.;Yuen, H. A.; Ngai, T. J.; Louie, S.G.; et al. (2003), SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo, Blood 101, 3597-3605.
56. Davies, H.; Bignell, G. R.; Cox, C.; Stephens, P.; Edkins, S.; et al. (2002), Mutations of the BRAF gene in human cancer, Nature 417, 949-954.
57. Eisen, T.; Ahmad, T.; Flaherty, K. T.; Gore, M.; Kaye, S.; et al. (2006), Sorafenib in advanced melanoma: A Phase II randomised discontinuation trial analysis, Br. J. Cancer 95, 581-586.
58. Ratain, M. J.; Eisen, T.; Stadler,W. M.; Flaherty, K. T.; Kaye, S. B.; et al. (2006), Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma, J. Clin. Oncol. 24, 2505-2512.
59. Llovet, J. M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; et al. (2008), Sorafenib in advanced hepatocellular carcinoma, New Engl. J. Med. 359, 378-390.
60. Giaccone, G. (2007), The potential of antiangiogenic therapy in non-small cell lung cancer, Clin. Cancer Res. 13, 1961-1970.
61. Henderson, Y. C.; Ahn, S. H.; Kang, Y.; Clayman, G. L. (2008), Sorafenib potently inhibits papillary thyroid carcinomas harboring RET/PTC1 rearrangement, Clin. Cancer Res, 14, 4908-4914.
62. Kloos, R. T.; Ringel, M. D.; Knopp, M. V.; Hall, N. C.; King, M.; et al. (2009), Phase II trial of sorafenib in metastatic thyroid cancer, J. Clin. Oncol, 27, 1675-1684.
63. Wilhelm, S.; Chien, D. S. (2002), BAY 43-9006: Preclinical data, Curr. Pharm. Design, 8, 2255-2257.
64. Wilhelm, S. M.; Carter, C.; Tang, L.;Wilkie, D.; McNabola, A.; et al. (2004),BAY43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis, Cancer Res. 64, 7099-7109.
65. Podar, K.; Tonon, G.; Sattler, M.; Tai, Y. T.; Legouill, S.; et al. (2006), The small-molecule VEGFreceptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma, Proc Natl. Acad. Sci. USA, 103, 19478-19483.
66. Kumar, R.; Knick, V. B.; Rudolph, S. K.; Johnson, J. H.; Crosby, R. M.; et al. (2007), Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity, Mol. Cancer Ther. 6, 2012-2021.
67. Sternberg, C. N.; Davis, I. D.; Mardiak, J.; Szczylik, C.; Lee, E.; et al. (2010), Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized phase III trial, J. Clin. Oncol, 28, 1061-1068.
68. Altork, N.; Guarino, M.; Lee, P.; et al. (2008), Preoperative treatment with Pazopanib (GW786034), a multikinase angiogenesis inhibitor in early-stage non-small cell lung cancer (NSCLC): a proof of concept phase II study, J. Clin. Oncol. 26(Suppl.), Abstract 7557.
69. Slamon, D. J.; Gomez, H. L.; Kabbinavar, F. F., (2008), Randomized study of pazopanib + lapatinib vs lapatinib alone in patients with HER2-positive advanced or metastatic breast cancer, J. Clin. Oncol. 26(Suppl.), Abstract 1016.
70. Friedlander, M.; Hancock, K. C.; Benigno, B.; et al. (2007), Pazopanib (GW786034) is active in women with advanced epithelial ovarian, phallopian tube and peritoneal cancers: Initial results of a phase II study, J. Clin. Oncol. 25(Suppl.), Abstract 5561.
71. Norden, A. D.; Drappatz, J.; Wen, P. Y. (2008), Antiangiogenic therapy in malignant gliomas, Curr. Opin. Oncol., 20, 652-661.
72. Sleijfer, S.; Ray-Coquard, I.; Papai, Z.; Le, C. A.; Scurr, M.; et al. (2009), Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma:Aphase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043), J. Clin. Oncol, 27, 3126-3132.
73. Schiller, J. H.; Larson, T.; Ou, S. H.; Limentani, S.; Sandler, A.; et al. (2009), Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study, J. Clin. Oncol, 27, 3836-3841.
74. Rini, B. I.;Wilding, G.; Hudes, G.; Stadler,W. M.; Kim, S.; et al. (2009), Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma, J. Clin. Oncol., 27, 4462-4468.
75. Kelly, R. J.; Rixe, O. (2010), Axitinib (AG-013736), Recent Results Cancer Res. 184, 33-44.
76. Wilmes, L. J.; Pallavicini, M. G.; Fleming, L. M.; Gibbs, J.; Wang, D.; et al. (2007), AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging, Magn Reson. Imag. 25, 319-327.
77. McCarty,M. F.;Wey, J.; Stoeltzing, O.; Liu,W.; Fan, F.; et al. (2004), ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor with additional activity against epidermal growth factor receptor tyrosine kinase, inhibits orthotopic growth and angiogenesis of gastric cancer, Mol. Cancer Ther. 3(9), 1041-1048.
78. Ciardiello, F.; Bianco, R.; Caputo, R.; Caputo, R.; Damiano, V.; et al. (2004), Antitumor activity of ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in human cancer cells with acquired resistance to antiepidermal growth factor receptor therapy, Clin. Cancer Res. 10, 784-793.
79. Yiin, J. J.; Hu, B.; Schornack, P. A.; Sengar, R. S.; Liu, K. W.; et al. (2010), ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain Mol. Cancer Ther. 9, 929-941.
80. Donis-Keller, H.; Dou, S.; Chi, D.; Carlson, K. M.; Toshima, K.; et al. (1993), Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC, Human Mol. Genet. 2, 851-856.