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Printable Handouts
Navigable Slide Index
- Introduction
- Overview
- Colon cancer cells - signaling mutations
- Molecular perturbations lead to cell biology changes
- Colon Cancer Cells – EGFR signalling
- EGFR-Family
- “Mr EGF”
- EGF/EGFR Family
- EGFR family and cancer
- Published research (1)
- Published research (2)
- Cancers & EGFR over-expression
- Targeting ErbB2 (HER-2) in breast cancer patients
- EGFR family – conundrums
- EGFR family structural biology
- EGF receptor extra-cellular domain (ECD) structure
- In 2003 our view of EGFR family signaling changed
- EGFR-ECD1-501 with TGF-α
- Ligand binding structure
- Model of the complete EGFR-ECD with ligand
- Analysis of cell surface EGFR ligand affinity
- ΔCR1-loop – loss of high affinity ligand binding
- Ligand induced conformational change
- Ligand dependent activation of the EGFR kinase
- ErbB2 and ErbB3 signaling
- ErbB2 1-509 3D structure
- Close contacts between domains in ErbB2 preclude ligand binding
- ErbB2
- The nature of the EGFR at the cell surface
- EGFR1-621 In solution
- EGFR1-621 in solution with ligand
- At the cell surface EGFR is complicated
- EGFR on the cell surface
- EGFR on the cell surface with ligand
- Probing changes in conformation
- Ligand induced conformational change on the cell surface
- Inside-out signaling
- EGFR-ICD mutants can activate the kinase
- EGFR oligomerization and kinase activation
- EGFR oligomerization and kinase activation diagram
- Detecting EGFR dimer oligomerization
- EGFR family signaling
- EGFR MAPK
- EGFR-PI3 kinase signaling
- EGFR-YAP signalling interactions
- E-cadherin
- EGFR and E-cadherin
- EGFR–Src
- ErbB2 and ErbB3 signaling
- EGFR – cancer biology
- Mutant EGFR induces resistance to cytotoxic drugs
- EGFR inhibitor induces apoptosis in the presence of CDDP
- Cisplatin + EGFR inhibitor treatment
- Temozolomide + EGFR inhibitor treatment
- mAb806
- Treatment of A431 xenografts with mAb806 and AG-1478
- Treatment of A431 xenografts with mAb806 and mAb528
- Benefit to colorectal cancer patients
- Treatment with dual inhibitors of signaling from the EGFR family
- MCLA-128 targets HER2 and HER3
- Anti-EGFR drug conjugate
- EGFR - antibody movie
- Dedication
- Acknowledgements
- Further reading
- Thank you for listening!
Topics Covered
- EGFR family members and cancer
- EGFR signalling in the oncogenic processes
- EGFR family structural biology
- ErbB2 and ErbB3 signalling
- EGFR dimer oligomerization
- PI3 kinase pathway
- E-cadherin
- EGFR inhibitors and antagonists
- Colon cancer treatments
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Burgess, T. (2021, February 25). EGF receptor family: targets for improving cancer therapy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 23, 2024, from https://doi.org/10.69645/SMLL9346.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
A selection of talks on Oncology
Transcript
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0:00
My name is Tony Burgess.
I'm a Laboratory Head at the Walter and Eliza Hall Institute in Melbourne.
My talk today will be about the EGF receptor family targets for improving cancer therapy.
0:14
This talk will cover a set of mutations relevant to the EGF receptor,
that drive cancer biology.
We will focus on the EGF receptor family and its ligands,
how they were discovered to be involved in cancer and then
some of the modern aspects of EGF receptor biology,
such as the way the receptor moves on the cell surface to provide
the intracellular signaling for driving cells into proliferation.
We will also be looking at the targeting,
the EGF receptor family members so we can improve cancer treatment,
in particular, how the different EGF receptor pathway
targeting drugs should be able to work together to improve outcomes for cancer patients.
0:58
Most colon cancers are initiated by mutations to the tumor suppressor genes, APC and p53.
These mutations are followed by several other mutations to signaling molecules,
in particular, the ras oncogene, integrins,
intracellular matrix overproduction, DNA repair enzymes such as MLH1,
and in our case, the EGF receptor,
which is sometimes over-expressed through amplification,
and at other times activated by truncation of
the N-terminus or mutations in the kinase domain.
All of these perturbations combine to drive cancer cells from
normal proliferation to abnormal lifetime and cell production in tissues.