Part2 Hallamarks

Question 1

BCR-ABL fusion

Answer 1

Consitutive active Tyrosine Kinase

Question 2

Development of Imatinib (Gleevec) for Chronic Myeloid Leukaemia (CML)

Answer 2

Aimed to block fusion protein • 80% of patients showed disappearance of cells carrying Philadelphia chromosome

Imatinib (gleevec) is an inhibitor of constitutive active tyrosine kinase BCR-ABL. Imatinib has improved the % survival chance of CML patients to over 90%.

Question 3

oncogenes

Answer 3

Their wild-type precursors participate in signalling for cell growth and proliferation, but their activity is tightly regulated in normal cells and in cancer cells they further activate these genes •

They promote growth/cell cycle entry at G1/S when activated

• Generally, mutation of a single copy in cancer cells is sufficient (the mutated variant is dominant)
• Genetic changes in neoplasms cause dominant gain of function
• overexpression or constitutive activation
• various mechanisms
• This results in uncontrolled proliferation
• The mutant proteins are found specifically in cancer cells, and are (potential) targets for drug therapy
• Examples include EGF-R, Ras, Myc, Src, Bcr-Abl

Question 4

Normal regulation of the cell cycle Extrinsic Regulation

Answer 4

Extrinsic regulation: 

Allows cell cycle to respond to external cues that promote cell growth and division

 Allows cell cycle to be inhibited when new cells are not needed

Question 5

Normal regulation of the cell cycle Intrinsic Regulation

Answer 5

Intrinsic regulation 

Orchestrates the sequence of events to ensure faithful replication of DNA and distribution into daughter cells: 
Key players include cyclins, Cdk’s, and their activators  Key regulated stages are G1/S, G2/M, and metaphase/anaphase 

Progression is inhibited if criteria are not met 

Apoptosis is triggered if damage is excessive

Question 6

Is cancer a genetic Disease ?

Answer 6

Is cancer a genetic disease? Yes. Always genetic but not always inherited.

Question 7

How does the C arise ?

Answer 7

Genetic and epigenetic mutations in oncogenes and tumor-suppressor genes •

Question 8

Which genes, when mutated, can give rise to cancer?

Answer 8

Oncogenes and Tumor suppressor genes

Question 9

Which of these can be an oncogene?

Answer 9

A) C-myc Yes 

B) RB NO 

C) cdk YES 

D) RAS YES 

E) MAPK YES

Question 10

Summary

Answer 10

Cancer is a genetic disease due to genetic and epigenetic mutations in genes known as oncogenes and tumor suppressor genes 

Cancer characteristics include: immortality, independence from growth/death cues, capacity of invasion, metastasis, escape to immune system. 

Cell cycle and apoptosis are severely deregulated in cancer. 

Oncogenes regulate cell cycle entry and survival 

Examples of oncogenes: RAS, EGFR, MAPK, BCR-ABL