Oncogenes

Question 1

What is the difference between targeted therapies and chemotherapy?

Answer 1

Targeted cancer therapies block the growth and spread of cancer by interfering with specific molecules involved in the growth, progression and spread of cancers.
Whereas
Chemotherapeutic drugs target rapidly dividing cancer cells and normal cells. (cytotoxic)

Question 2

What are oncogenes?

Answer 2

A proto-oncogene that has been activated by mutation or overexpression

Question 3

What are proto-oncogenes?

Answer 3

Normal cellular genes that regulate cell growth and/or division and differentiation.

Question 4

The two main types of conversion from proto-oncogene to oncogene is:

Answer 4

• Mutation in the gene results in different oncoprotein to the normal protein within the cell
• Oncoproteins are the same as normal protein but expressed at higher levels

Question 5

Oncogene activation mechanisms:

Give examples

Answer 5

Point mutation: KRAS in lung cancer
Gene amplification: c-myc in breast cancer
Chromosomal translocation: Fusion protein creation - BCR-ABL in chronic myeloid leukaemia (CML)
and disruption of regulatory elements

Question 6

What is HER2?

About HER2:

Answer 6

Gene that encodes for part of the human epidermal growth factor receptor 2

Receptor dimerisation is required for HER2 function

HER2 is a protein that has intracellular tyrosine kinase activity

HER2 is applied in 20% of invasive breast cancers + associated with aggressive disease and poor prognosis

Question 7

HER2 targeted therapies

Answer 7

Trustuzumab & Pertuzumab are monoclonal antibodies that target HER2 (effective only for HER2 +ve cancers)

Question 8

What is RAS?

Answer 8

RAS proteins are cellular signal transducers
Activation of receptor tyrosine kinase activates the RAS proteins

Ras gene products are involved in kinase signalling pathways. control the transcription of genes which regulates cell growth and differentiation

Question 9

When is KRAS active and inactive?

Answer 9

Active when GTP is bound

Inactive when GTP breaks up -> GDP

Question 10

Effect of KRAS mutations?

Answer 10

KRAS isn’t responsive to targeted therapies
It is affected by point mutations

Mutations of KRAS; permanently switched on (bound to GTP) (= permanent cell growth + proliferation)
Permanent activation of the protein (tyrosine kinase)

Question 11

BCR-ABL 1 can indicates?

Answer 11

Chronic myeloid leukaemia

BCR-ABL1 -> Philadelphia chromosome

Question 12

What does BCR encode for?

What does ABL encode for?

Answer 12

BCR encodes a protein that acts as a guanine nucleotide

ABL encodes a protein tyrosine kinase.

Question 13

BCR-ABL1 mutation occurs as a result of:

Answer 13

ABL : chromosome 9
BCR : chromosome 22

translocation

Question 14

What is the result of unregulated BCR-ABL?

Answer 14

Tyrosine kinase activity causes:

• Proliferation of progenitor cells in absence of growth factors
• Decreased apoptosis

Question 15

Therapeutic targets/applications of BCR-ABL1 mutations

Answer 15

Imatinib specifically inhibits BCR-ABL1 (mutation)

Question 16

What is myc?

Answer 16

Family of genes that encodes for transcription factors

Question 17

Pathogenic alterations in c-myc involves:

Answer 17

Amplifications and translocations

Question 18

Translocation between which chromosomes are observed in Burkitt’s syndrome

Answer 18

Chromosome 8 (c-myc proto-oncogene) and chromosome 14 (immunoglobulin heavy chain gene)

Question 19

C-myc therapeutic applications

Answer 19

Translation inhibitors
Myc protein destabilising drugs

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