week 6 Flashcards
Genes for Malignant melanoma
BRAF
Codon 600
drugs for Malignant melanoma
Vemurafenib,
Dabrafenib,
Trametinib
drug action for Malignant melanoma
ATP-competitive inhibitor of kiase domain of BRAF
consequnce of identifying mutation for Malignant melanoma
Drug targets BRAF mutated at codon 600
Genes for Non small cell lung cancer
EGFR
Exons 18,19,20 and 21
drugs for Non small cell lung cancer
Gefitinib, Erlotinib, Afatinib, Dacomitinib
drug action for Non small cell lung cancer
EGFR Tyrosine kinase inhibitor
consequence of identifying mutation for Non small cell lung cancer
Drug targets EGFR over activity caused by mutation in the Tyrosine kinase domain of EGFR
drugs for Non small cell lung cancer
ALK
Crizotinib, Ceritinib, Alectinib
drug action for Non small cell lung cancer
ALK
Crizotinib, Ceritinib, Alectinib
Receptor tyrosine kinase inhibitor (including ALK and Met)
consequence for identifying mutations Non small cell lung cancer
ALK
Lung cancers can have the EML4-ALK translocation. This translocation causes ligand-independent dimerization and/or oligomerization of ALK, resulting in constitutive kinase activity
gene for Breast cancer
HER2
drug for Breast cancer
Herceptin
drug action for Breast cancer
Antibody to HER2 receptors blocking downstream signalling
consequence of identifying mtuation for Breast cancer
Breast cancers have to be positive for HER2 to work.
gene for Colorectal cancer
KRAS CODONS 12, 13, 59, 61 117 AND 146 NRAS CODONS 12,13, 59 and 61
drug for Colorectal cancer
Cetuximab and panitumumab
drug actionfor Colorectal cancer
Antibody to EGFR receptors blocking downstream signalling
consequence of identifyign mutation Colorectal cancer
If patient has a downstream RAS mutation blocking the EGFR will be ineffective
how is cancer a genomci disease
More and more mutations build up so not accurate replication and end up changing some hallmarks of cancer
CML drug treats
Imatinib
casue of CML
BCR-ABL1 fusion gene produced by trsanlocation
95% by (9;22) (q34;11) translocation
creates constitutively active tyrosine kinase leading to ucnrontrolled proliferation
normal action of ABL1
ABL1 is tyrosine kinase- normall role in differentiation and reg of cell cycle
imatinib action
blocks ATP binding centre of BCR-ABL so inhibits phosphorylation activity so less cancer protein produced
effect of inbiting BRAF
no activation of MEK so no ERK so down cell prolif and survival
Ras-RAf pathway
growth factor binds-
receptor tyrosine kinase activated- Ras activated-
BRAf activated,
Mek then Erk activated so normal cell prolif and survival
EGFR pathway
EGFR receptor activated KRAS,NRAS activated, activate RAF, MEK, ERK, trans factors, proliferation and survival
Ras swithcing
Gdp is on GTP is off controlled by GEFs- guanine nucleotide exchange fact (sos1SOS2
mechanism of GAOS
terminate On state by catalyzing hydrolysis of GTP to GDP
waht is Gastrointestinal stromal tumours (GISTT
Sarcoma- tumour of soft tissue
mutation in Gastrointestinal stromal tumours (GISTT
Caused by mutations in Kit and PDGFRA (receptor tyrosine kinase) so constitutive downstream pathways
treatment of Gastrointestinal stromal tumours (GISTT
Imatinib bits of ATP bidnign sites of KIT and PDGFRA and bcr-abl inactivating signalling
Mek-Erk for proliferation and PI3K for survival
or Sunitinib is multi target TKI
