EGFR signalling And Cancer Flashcards
What do ERbB receptors undergo?
Autophosphorylation
EGFR signal transduction
GRB2 SOS RAS RAF MEK MAPK
3 ways EGFR enters cells
Clathrin dep endocytosis
Clathrin indep endocytosis
Secretase cleavage
3 ways EGFR signalling is enhanced
Increase in amount of ligand available for binding
Cross talk between receptors
Heterodimerisation with other members of HER family
How many RTKs in mammals?
58
How many subfamilies of RTKs?
20
Regions of RTK
Variable extra cellular region
Well conserved TK region
RTK mutation in cancer -percentage
30%
EGFR main biological function
Epithelial development
Neuronal differentiation
cKit main biological function
Haematopoiesis
Mast cell development
HGFR role
Placenta, liver and muscle development
RET role
Kidney and neuronal differentiation
How many percent of human cancers have overexpressed EGFR?
50%
5 results of overexpressed EGFR in cancer
Dedifferentiation Angiogenesis Metastasis Cell proliferation Survival and protection from apoptosis
Which antibody blocks ligand binding to EGFR?
Cetuximab
2 antibodies blocking dimerisation of ErbB2
Pertuzumab
Trastuzumab
What are the majority of TKI?
ATP mimetic
2 EGFR specific TKI;
Gefitinib
Erlotinib
A EGFR/ERbB2 inhibitor
Lapatinib
Direct action of mAB cancer therapy 2
Block cell cycle progression, antiangiogenic, internalising receptors
Conjugation with toxins
Indirect action of mAB cancer therapy
Immune system cytotoxicity
Ab dep cellular cytotoxicity
What does imatinib do?
Small molecule inactivating kinase activity of BCR-abl and multi targeted inhibitor of KIT and PDGFA, PDGFB
