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Biology of Cancer SSC > Cell Signalling and Oncogenes > Flashcards

Cell Signalling and Oncogenes Flashcards

1
Q

What do all signalling pathways involve?

A

A chemical messenger, a receptor, and a cellular response.

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2
Q

Name some rapidly dividing cells

A

epithelia, blood cells

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3
Q

Name some slowly dividing cells

A

nerve cells

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4
Q

What can signal transduction result in?

A

Alterations in:
Cell metabolism
Gene transcription
Cell shape

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5
Q

What are proto-oncogenes?

A

Genes that code proteins that help regulate cell growth and differentiation

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6
Q

What is an oncogene?

A

A proto-oncogene that has become activated due to mutation or increased expression

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7
Q

What are the two factors in increasing genetic instability?

A

Oncogene activation

Tumour suppressor gene inactivation

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8
Q

What are the main initiating agents for cancer?

A

Environment

Genetic susceptibility

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9
Q

What do oncogene activation and tumour suppressor gene inactivation lead to?

A

Replicative senescence
Programmed cell death
Differentiation
Cell cycle checkpoint control

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10
Q

What are the main mutations in cancer?

A

Deletion, insertion, substitution, amplification and translocation

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11
Q

What can be deleted?

A

Base pair(s)
Gene
Chromosome

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12
Q

What can be inserted?

A 
Base pair(s)
Novel insertion of viral DNA
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13
Q

What can be substituted?

A

Base pair(s)

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14
Q

What can be amplified?

A

Gene
Region
Chromosome

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15
Q

What can be translocated?

A

Chromosome

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16
Q

What proteins are encoded by oncogenes that act on cell surface receptors?

A

Growth factors e.g. PDGF

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17
Q

What proteins are encoded by oncogenes that act on intracellular proteins due to extracellular signalling?

A

Growth factor receptors e.g. EGF receptor (erbB)

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18
Q

What proteins are encoded by oncogenes that are activated by transmembrane receptors?

A

Protein kinases or proteins that activate protein kinases e.g. Ras (ras), Raf (raf), Src (src)

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19
Q

What proteins are encoded by oncogenes that act within the cell?

A

Proteins that control the cell cycle e.g Cyclin D (bcl-1)

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20
Q

What proteins are encoded by oncogenes that regulate cell survival?

A

Proteins that affect apoptosis e.g. Bcl-2 (bcl-2)

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21
Q

What proteins are encoded by oncogenes that act on DNA?

A

Transcription factors e.g. Myc (myc)

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22
Q

Give 2 examples of insertional mutagenesis caused viruses?

A

Human papillomavirus 16/18 and cervical cancer

Hepatitis B virus and hepatocellular cancer

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23
Q

How common is insertional mutagenesis?

A

Relatively uncommon in human cancer, but has 2 high profile examples.

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24
Q

What chromosomal translocation occurs in chronic myeloid leukaemia?

A

9;22 (c-abl (9) truncated onto bcr (22))

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25
What effect does the 9;22 CML translocation have?
Fusion protein has abnormal tyrosine kinase activity
26
What chromosomal translocation occurs in Burkitt's lymphoma?
8;14 (c-myc (8) truncated onto igh (14))
27
What effect does the 8;14 Burkitt's lymphoma have?
Stronger promotion of c-myc gene leading to constitutive MYC expression in B cells (gene at 14q32 = IgH locus enhancer)
28
How can chromosomal amplification be visualised?
FISH (n-myc amplification in neuroblastoma)
29
What is the main example of point mutation?
RAS gene family
30
At which codons can RAS genes be found to be activated by mutations?
12, 13 and 61.
31
Are ras mutations gain or loss of function?
Gain
32
What do ras genes ultimately effect?
Transcriptional regulation
33
Which ras is most commonly activated/mutated?
Ki-ras (12p)
34
What activate the ras protein?
Receptor tyrosine kinases
35
What kind of proteins are ras proteins?
GTP-binding monomeric switch proteins
36
What binds to ras to activate it?
GTP
37
What signalling pathway does ras activation activate?
MAP kinase pathway
38
What does the type of ras mutation determine?
prognosis in colorectal cancer
39
Which ras mutation has been associated with increased risk of recurrence and death in Dukes C?
KRAS mutation Gly12Val (G->T)
40
How must KRAS mutation be interpreted?
In the context of other molecular and signalling abnormalities
41
Why can't RAS be blocked therapeutically?
It has widespread functions in the body so complications will occur
42
Give an example of where RAS is part of an important pathway
Synapic remodelling in the brain
43
What percentage of metastatic melanomas have a BRAF mutation?
~50%
44
What makes up 80% of these BRAF mutations?
V600E
45
What makes up 16% of these BRAF mutations?
V600K
46
What makes up 3% of these BRAF mutations?
V600R
47
When do these BRAF mutations often arise?
Early on - found in benign nevi.
48
Can BRAF mutations be found in other tumour types?
Yes
49
What is Vemurafenib?
BRAF inhibitor
50
Why is it called Vemurafenib?
V600E mutant Raf inhibitor - V E mu raf in
51
What gene is amplified in 10-30% of human breast cancers?
erbb2
52
What does the gene erbb2 code for?
HER-2 (Human epidermal growth factor receptor 2)
53
Which protein is over expressed in 10-30% of human breast cancer?
HER-2
54
What percentage of human breast cancers is HER-2 amplification linked with?
10-30%
55
What is HER-2 amplification linked to?
Poor prognosis
56
How can HER-2 amplification be detected?
FISH and immunohistochemistry
57
How is a HER-2 amplification linked breast cancer treated?
Drugs that bind to HER-2 and prevent growth
58
Give 2 examples of HER-2 antagonists
Trastuzumab (Herceptin) | Pertuzumab (Parjeta)
59
How many HER-2 receptors are there per cell in Her-2 positive breast cancer?
~1-2 million
60
What is trastuzumab (herceptin)?
Monoclonal antibody
61
When is trastuzumab given?
Often with chemo, but also alone as a prophylactic
62
What is trastuzumab used to treat?
Early- and late- stage breast cancer
63
What is pertuzumab (perjeta)?
Monoclonal antibody
64
When is pertuzumab given?
With trastuzumab and chemo
65
What is pertuzumab used to treat?
As a neoadjuvant therapy with early stage breast cancer, or to treat advanced breast cancer
66
What therapy is used to treat advanced breast cancer in women who have already been treated with trastuzumab and chemo?
Ado-trastuzumab emtansine (TDM-1)
67
What is Lapatinib?
A kinase inhibitor
68
What is Lapatinib used for?
Treating advanced breast cancer when trastuzumab is no longer working

Biology of Cancer SSC (16 decks)

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