week 6

Question 1

Genes for Malignant melanoma

Answer 1

BRAF

Codon 600

Question 2

drugs for Malignant melanoma

Answer 2

Vemurafenib,
Dabrafenib,
Trametinib

Question 3

drug action for Malignant melanoma

Answer 3

ATP-competitive inhibitor of kiase domain of BRAF

Question 4

consequnce of identifying mutation for Malignant melanoma

Answer 4

Drug targets BRAF mutated at codon 600

Question 5

Genes for Non small cell lung cancer

Answer 5

EGFR

Exons 18,19,20 and 21

Question 6

drugs for Non small cell lung cancer

Answer 6

Gefitinib, Erlotinib, Afatinib, Dacomitinib

Question 7

drug action for Non small cell lung cancer

Answer 7

EGFR Tyrosine kinase inhibitor

Question 8

consequence of identifying mutation for Non small cell lung cancer

Answer 8

Drug targets EGFR over activity caused by mutation in the Tyrosine kinase domain of EGFR

Question 9

drugs for Non small cell lung cancer

ALK

Answer 9

Crizotinib, Ceritinib, Alectinib

Question 10

drug action for Non small cell lung cancer

ALK

Answer 10

Crizotinib, Ceritinib, Alectinib

Receptor tyrosine kinase inhibitor (including ALK and Met)

Question 11

consequence for identifying mutations Non small cell lung cancer
ALK

Answer 11

Lung cancers can have the EML4-ALK translocation. This translocation causes ligand-independent dimerization and/or oligomerization of ALK, resulting in constitutive kinase activity

Question 12

gene for Breast cancer

Answer 12

HER2

Question 13

drug for Breast cancer

Answer 13

Herceptin

Question 14

drug action for Breast cancer

Answer 14

Antibody to HER2 receptors blocking downstream signalling

Question 15

consequence of identifying mtuation for Breast cancer

Answer 15

Breast cancers have to be positive for HER2 to work.

Question 16

gene for Colorectal cancer

Answer 16

KRAS CODONS 12, 13, 59, 61 117 AND 146 NRAS CODONS 12,13, 59 and 61

Question 17

drug for Colorectal cancer

Answer 17

Cetuximab and panitumumab

Question 18

drug actionfor Colorectal cancer

Answer 18

Antibody to EGFR receptors blocking downstream signalling

Question 19

consequence of identifyign mutation Colorectal cancer

Answer 19

If patient has a downstream RAS mutation blocking the EGFR will be ineffective

Question 20

how is cancer a genomci disease

Answer 20

More and more mutations build up so not accurate replication and end up changing some hallmarks of cancer

Question 21

CML drug treats

Answer 21

Imatinib

Question 22

casue of CML

Answer 22

BCR-ABL1 fusion gene produced by trsanlocation
95% by (9;22) (q34;11) translocation
creates constitutively active tyrosine kinase leading to ucnrontrolled proliferation

Question 23

normal action of ABL1

Answer 23

ABL1 is tyrosine kinase- normall role in differentiation and reg of cell cycle

Question 24

imatinib action

Answer 24

blocks ATP binding centre of BCR-ABL so inhibits phosphorylation activity so less cancer protein produced

Question 25

effect of inbiting BRAF

Answer 25

no activation of MEK so no ERK so down cell prolif and survival

Question 26

Ras-RAf pathway

Answer 26

growth factor binds- receptor tyrosine kinase activated- Ras activated- BRAf activated, Mek then Erk activated so normal cell prolif and survival

Question 27

EGFR pathway

Answer 27

``` EGFR receptor activated KRAS,NRAS activated, activate RAF, MEK, ERK, trans factors, proliferation and survival ```

Question 28

Ras swithcing

Answer 28

Gdp is on GTP is off controlled by GEFs- guanine nucleotide exchange fact (sos1SOS2

Question 29

mechanism of GAOS

Answer 29

terminate On state by catalyzing hydrolysis of GTP to GDP

Question 30

waht is Gastrointestinal stromal tumours (GISTT

Answer 30

Sarcoma- tumour of soft tissue

Question 31

mutation in Gastrointestinal stromal tumours (GISTT

Answer 31

Caused by mutations in Kit and PDGFRA (receptor tyrosine kinase) so constitutive downstream pathways

Question 32

treatment of Gastrointestinal stromal tumours (GISTT

Answer 32

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