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1. Introduction
2. Colon cancer cells -signaling mutations (1)
3. Colon cancer cells -signaling mutations (2)
4. Colon cancer cells -signaling mutations (3)
5. Molecular perturbations lead to changes in:
6. EGFR system
7. "Mr. EGF"
8. Incidence of cancers and EGFR over-expression
9. EGFR and cancer responsiveness to inhibitors
10. EGF receptor signaling
11. EGF receptor family ECD 3D structures
12. EGF/EGFR family>8 ligands and 4 receptors
13. EGF receptor and cancer
14. EGFR conundrums
15. EGF receptor extra-cellular domain (ECD) structure
16. Analysis of cell surface EGFR ligand affinity
17. Extra-cellular domain constructs (ECD) for EGFR
18. Comparison of EGFR ECD and st-EGFR
19. Elucidating the 3D-structure
20. EGF receptor crystal structure
21. Single receptor subunit
22. Binding of ligand
23. The back-to-back dimer
24. Delta-CR1-loop and loss of high-affinity binding
25. Structure for the full-length EGFR-ECD
26. But there was another twist:
27. HER3 ECD: Leahy and Cho, Science 2002
28. EGF complex formed at low pH
29. EGF receptor1-621:TGF-a crystal structure, pH5
30. erbB2
31. erbB21-509 3D- structure
32. erbB2 is closely packed
33. The EGF receptor fulcrum
34. The erbB2 hinge region
35. The erbB2 CR1 domain
36. The negative electrostatic field of erbB2
37. erbB2 "full-length" ECD
38. ErbB2...
39. Current view of activation mechanism (1)
40. Current view of activation mechanism (2)
41. EGF receptor activation movie
42. The nature of the EGFR at the cell surface
43. At the cell surface EGFR is complicated
44. EGFR1-621 In solution:
45. EGFR1-621 in solution with ligand:
46. On the cell surface
47. On the cell surface in the presence of ligand
48. Epitope for mab 806
49. Untethering of EGFR on the cell surface
50. EGFR inhibitors synergize with cytotoxic drugs
51. Mutant EGF receptor induces resistance
52. U87MG-delta(2-7)-EGFR cells in vitro
53. U87MG-delta(2-7)-EGFR xenografts
54. Optimization of the EGFR inhibitor
55. U87MG-delta(2-7) -EGFR xenografts
56. Antibody mab 806 has specificity for delta-EGFR
57. Treatment of xenografts with delta-806 Mab
58. Treatment xenografts with mAbs 806 and 528
59. Delta-2-7 EGFR is spontaneously active
60. EGFR inhibitors and antagonists in humans
61. Our current research includes :
62. Collaborators
63. Further reading

Topics Covered

• The association of the Epidermal Growth Factor Receptor (EGFR) with the tumorigenic state
• The four related members of the EGFR family (EGFR, erbB2, erbB3 and erbB4)
• Signaling of the activated receptors as either homo- or heteromeric oligomers
• Activation of the EGFR by excess ligand stimulation, receptor over-expression and/or mutation in many carcinomas
• Utility of antibodies and receptor kinase inhibitors which interfere with signaling from the EGFR family as agents in cancer therapy
• The three-dimensional structures for the extracellular domains of EGFR, erbB2, erbB3 and erbB4 and the discovery that EGFR, erbB3 and erbB4 undergo major conformational transitions when interacting with their ligands
• Development of antibodies (mab806) which reduce tumor formation from cells expressing either truncated D2-7 EGFR or over-expressed EGFR by binding to the receptor in a region normally masked by the dimerization of the EGFR extracellular domain
• Use of EGFR antagonists or inhibitors to increase tumor killing by cytotoxic anti-cancer drugs and/or radiation
• Improvement of tumor killing by combining EGFR antagonists and EGFR kinase inhibitors

Links

Series:

• Signal Transduction via Protein Tyrosine Kinase Receptors

Categories:

• Cancer
• Pharmaceutical Sciences

Therapeutic Areas:

• Oncology

Talk Citation

Burgess, T. (2007, October 1). EGF receptor family: targets for cancer therapeutics [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 23, 2024, from https://doi.org/10.69645/ALFD7906.
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Publication History

• Published on October 1, 2007
• Archived on February 25, 2021

Financial Disclosures

• There are no commercial/financial matters to disclose.