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1. Introduction
2. Protein tyrosine kinases (TKs)
3. Phosphorylation of tyrosine residues
4. Two classes of TKs
5. Nonreceptor TKs
6. Receptor TKs (1)
7. Receptor and nonreceptor TKs
8. Receptor TKs (2)
9. Activation of receptor TKs
10. The effects of rTK activation
11. Mechanisms of TK dysregulation in cancer
12. Consequences of TK activation in cancer
13. Strategies to target TKs in cancer therapy
14. CML- a model disease for science advancement
15. Chronic myeloid leukaemia (CML)
16. 1960 - discovery of the Philadelphia chromosome
17. 1973 - the first description of human oncogene
18. 1990- BCR-ABL causes CML in mice
19. Imatinib specifically targets BCR-ABL oncogene
20. Imatinib mesylate (1)
21. Imatinib mesylate (2)
22. Imatinib- the IRIS trial
23. Targeting other rTKs
24. rTK dysregulation in cancer
25. Mutations in rTKs lead to constitutive activation
26. Epidermal growth factor receptor (EGFR)
27. Small molecule inhibitors of EGFR
28. Factors predicting response to EGFR TK inhibitors
29. Cetuximab
30. Her-2/neu
31. Herceptin
32. C-KIT
33. PDGFR
34. Sites of KIT and PDGFR alpha mutations in GIST
35. Treatment paradigms for the treatment of GIST
36. Imatinib targets in solid tumours
37. FLT3: a major target in AML
38. Direct inhibitors of FLT3
39. C-MET
40. Small-molecule MET inhibitors
41. Vascular endothelial growth factor (receptor)
42. Completed anti-VEGF therapy phase III trials
43. Bevacizumab
44. Fibroblast growth factor receptor 3 (FGFR 3)
45. Other TK targets in hematologic malignancies
46. Simultaneous inhibition of two TKs
47. Vandetanib (ZD6474) and AZD2171
48. Multitargeted TKIs: sunitinib malate
49. Biological effects of sunitinib
50. Properties of sunitinib malate
51. Multitargeted TKIs: sorafenib
52. Limitations of TK therapy: toxicity
53. The unexpected cardiotoxicity of imatinib
54. Limitations of TK therapy: resistance
55. Limitations of TK therapy: resistance to mAbs
56. Problems with imatinib
57. Mechanisms of resistance to TKI therapy
58. The development of resistance to imatinib
59. Imatinib-resistant mutations in BCR-ABL
60. Resistance mechanism
61. T315I - "the mutation from hell"
62. BMS-354825 (dasatinib)
63. Imatinib resistant CML cells
64. Overcoming resistance
65. Identifying new targets
66. The drug development process for TKIs
67. Targeted therapy in haematological malignancies
68. Targeted therapy in solid tumours
69. Summary

Topics Covered

• Overview of tyrosine kinases
• Tyrosine kinase dysregulation in cancer
• The example of chronic myelogenous leukemia
• Receptor tyrosine kinases: function and involvement in cancer, treatment with small molecule inhibitors to these tyrosine kinases
• Inhibition of several tyrosine kinases
• Toxicity
• Resistance
• The future of treatment with tyrosine kinase inhibitors

Links

Series:

• Cancer Therapy

Categories:

• Biochemistry
• Cancer
• Diseases, Disorders & Treatments
• Pharmaceutical Sciences

Therapeutic Areas:

• Oncology

Talk Citation

Publication History

• Published on June 16, 2009
• Reviewed on December 4, 2019

Financial Disclosures

• Dr. Daniela Krause has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.