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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
Q

What effect does the 9;22 CML translocation have?

A

Fusion protein has abnormal tyrosine kinase activity

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26
Q

What chromosomal translocation occurs in Burkitt’s lymphoma?

A

8;14 (c-myc (8) truncated onto igh (14))

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27
Q

What effect does the 8;14 Burkitt’s lymphoma have?

A

Stronger promotion of c-myc gene leading to constitutive MYC expression in B cells (gene at 14q32 = IgH locus enhancer)

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28
Q

How can chromosomal amplification be visualised?

A

FISH (n-myc amplification in neuroblastoma)

29
Q

What is the main example of point mutation?

A

RAS gene family

30
Q

At which codons can RAS genes be found to be activated by mutations?

A

12, 13 and 61.

31
Q

Are ras mutations gain or loss of function?

A

Gain

32
Q

What do ras genes ultimately effect?

A

Transcriptional regulation

33
Q

Which ras is most commonly activated/mutated?

A

Ki-ras (12p)

34
Q

What activate the ras protein?

A

Receptor tyrosine kinases

35
Q

What kind of proteins are ras proteins?

A

GTP-binding monomeric switch proteins

36
Q

What binds to ras to activate it?

A

GTP

37
Q

What signalling pathway does ras activation activate?

A

MAP kinase pathway

38
Q

What does the type of ras mutation determine?

A

prognosis in colorectal cancer

39
Q

Which ras mutation has been associated with increased risk of recurrence and death in Dukes C?

A

KRAS mutation Gly12Val (G->T)

40
Q

How must KRAS mutation be interpreted?

A

In the context of other molecular and signalling abnormalities

41
Q

Why can’t RAS be blocked therapeutically?

A

It has widespread functions in the body so complications will occur

42
Q

Give an example of where RAS is part of an important pathway

A

Synapic remodelling in the brain

43
Q

What percentage of metastatic melanomas have a BRAF mutation?

A

~50%

44
Q

What makes up 80% of these BRAF mutations?

A

V600E

45
Q

What makes up 16% of these BRAF mutations?

A

V600K

46
Q

What makes up 3% of these BRAF mutations?

A

V600R

47
Q

When do these BRAF mutations often arise?

A

Early on - found in benign nevi.

48
Q

Can BRAF mutations be found in other tumour types?

A

Yes

49
Q

What is Vemurafenib?

A

BRAF inhibitor

50
Q

Why is it called Vemurafenib?

A

V600E mutant Raf inhibitor - V E mu raf in

51
Q

What gene is amplified in 10-30% of human breast cancers?

A

erbb2

52
Q

What does the gene erbb2 code for?

A

HER-2 (Human epidermal growth factor receptor 2)

53
Q

Which protein is over expressed in 10-30% of human breast cancer?

A

HER-2

54
Q

What percentage of human breast cancers is HER-2 amplification linked with?

A

10-30%

55
Q

What is HER-2 amplification linked to?

A

Poor prognosis

56
Q

How can HER-2 amplification be detected?

A

FISH and immunohistochemistry

57
Q

How is a HER-2 amplification linked breast cancer treated?

A

Drugs that bind to HER-2 and prevent growth

58
Q

Give 2 examples of HER-2 antagonists

A

Trastuzumab (Herceptin)

Pertuzumab (Parjeta)

59
Q

How many HER-2 receptors are there per cell in Her-2 positive breast cancer?

A

~1-2 million

60
Q

What is trastuzumab (herceptin)?

A

Monoclonal antibody

61
Q

When is trastuzumab given?

A

Often with chemo, but also alone as a prophylactic

62
Q

What is trastuzumab used to treat?

A

Early- and late- stage breast cancer

63
Q

What is pertuzumab (perjeta)?

A

Monoclonal antibody

64
Q

When is pertuzumab given?

A

With trastuzumab and chemo

65
Q

What is pertuzumab used to treat?

A

As a neoadjuvant therapy with early stage breast cancer, or to treat advanced breast cancer

66
Q

What therapy is used to treat advanced breast cancer in women who have already been treated with trastuzumab and chemo?

A

Ado-trastuzumab emtansine (TDM-1)

67
Q

What is Lapatinib?

A

A kinase inhibitor

68
Q

What is Lapatinib used for?

A

Treating advanced breast cancer when trastuzumab is no longer working

Biology of Cancer SSC (16 decks)

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