Signal transduction 2

Question 1

BCR-ABL mimics what factor activation?

Answer 1

Growth factor

• Increased cell growth and inhibits autophagy(mTOR)
• decreased cell cycle arrest (FOXO)
• Inhibition of p53 (MDM2)
• Blocks BCL-2 (BAD)

Question 2

What is the basic design of a tyrosine kinase?

Answer 2

Ligand binding domane is extracellular
Tyrosine kinase domain in intracellular
- receptors only signal when dimerized

Question 3

What is SH2?

Answer 3

It is the reader

- allows aid in the signal transduction of receptor tyrosine kinase pathways

Question 4

What does BCR-ABL activate and when are they found active?

Answer 4

PI3K/AKT pathways.

- These pathways are commonly activated in human cancers.

Question 5

What is the regulation of PIP2 to PIP3?

Answer 5

This can be inhibited by phosphatase and tensin homolog (PTEN), a phosphatase that is down-regulated in many cancers

Question 6

What is HIFalpha?

Answer 6

Hypoxia inducible factor

Question 7

IN the presence of what is it broken down?

Answer 7

Prolyl hydroxylase which needs Vit C as cofactor

• O2
• alpha-ketoglutarate

Question 8

However when these are lacking what does HIFa do?

Answer 8

translocates to nucleus to increased induction of hypoxia inducible genes

• VEGF and PDGF
• Glut-1, EPO and IL-6

Question 9

What does VEGF bind to and what is its function?

Answer 9

VEGFR-2

• Endothelial cell proliferation
• Endothelial cell Migration
• Vascular permeability

Question 10

What are some VEGFR inhibitors side effects?

Answer 10

HTN

• hypothyroid
• loose hair pigment
• Rare but lethal- GI perf, Pericardial effusion, myelosuppresion, and hepatic toxicity

Question 11

What are some VEGF axis therapy?

Answer 11

Sorafenib
Sunitinib
INF-a/Bevacizumab
Axitinib

Question 12

What is the MOA of Bevacizumab?

Answer 12

Ab against VEGF- inhibits angiogeneis

- solid tumors like Colon cancer and RCC

Question 13

What are some side effects of Bevacizumab?

Answer 13

hemorrhage
blood clots
and impaired wound healing

Question 14

What is the MOA of Pazopanib and what does it fight against?

Answer 14

signal transduction inhibitor, TKI

- RCC

Question 15

What is HER2?

Answer 15

aka Erb-B2

• member of the EGFR (epidermal growth factor receptor) family
• intracellular kinase activity but no ligand binding domain

Question 16

What is Trastuzumab and its MOA?

Answer 16

Signal transduction inhibitor that is an antibody against Her2 protein

• fights against Her2 expressing breast and GI cancers
• cardiac toxicity

Question 17

What is panitumumab?

Answer 17

Signal transductions inhibitor that fight against EGFR driven cancers of aerodigestive tract

Question 18

What is a common TKI against HER2?

Answer 18

Lapatinib

Question 19

What is erlotinib?

Answer 19

EGFR tyrosine kinase inhibitor

• non-small cell lung carcinoma
• rash

Question 20

what is cetuximab?

Answer 20

monoclonal ant-body against EGFR

• Colorectal and head/neck cancer
• rash, elevated LFTs and diarrhea

Question 21

where is it more common to see adenocarcinomas of lung with EGFR activation muation or activated ALK signaling?

Answer 21

young
female
asian
non-smokers

Question 22

what patients gene most likely respond and resistance against EGFR directed therapy?

Answer 22

Deletion on Exon 19 L858R

T790m Mutation

Question 23

What is Imatinib and what is its MOA?

Answer 23

Tyrosine kinase inhibitor of BCR-ABL

• fights against CML and gi stromal tumors
• fluid retention

Question 24

What is Ibrutinib and what is its MOA?

Answer 24

Signal transduction inhibitor, TKI

- B cell malignancies, CLL

Question 25

What is Crizotinib and what is its MOA?

Answer 25

Signal transduction inhibitor, TKI

• Lung cancer with ALK or ROS1 activation
• C-met over expressing thyroid cancers