Cell Signalling and Oncogenes Flashcards Preview

SSC- Biology of Cancer > Cell Signalling and Oncogenes > Flashcards

Flashcards in Cell Signalling and Oncogenes Deck (81)
1

What do cells respond to?

Specific chemicals that signal them to divide 

2

What do the pathways for cell signalling utilised by cells have in common? 

They all display the same fundamental characteristics 

3

What do all signalling pathways involve? 

  • Chemical messenger
  • Receptor
  • Cellular response

 

4

What is signal transduction? 

Essentially, the transmission of a signal from the outside of a cell to the nucleus 

 

5

What can the signal transduced from the outside of the cell to the inside result in? 

Alterations in cell metabolism, gene transcription, and/or cell shape 

6

What does alteration in gene transcription lead to? 

Changes in protein expression 

7

What are proto-oncogenes? 

Genes coding for proteins that help regulate cell growth and differentiation 

8

In what physiological process are proto-oncogenes fundamental? 

Homeostasis 

9

What happens to proto-oncogenes in malignancy? 

They become activated to an oncogene due to mutations, or increased expression 

10

Where is oncogene activation an important mechanism? 

In human cancers 

11

What are the types of mutations that can cause cancer? 

  • Deletion 
  • Insertion
  • Substitution
  • Amplification 
  • Translocation 

 

12

What can be deleted in mutations? 

  • Base pair(s)
  • Genes
  • Chromosomes 

 

13

What can be inserted in mutations? 

  • Repeats of base pair(s)
  • Novel insertions
  • Viruses

 

 

14

What can be substituted in mutations?

Base pairs . 

15

What can be amplified in mutations? 

  • Genes
  • Regions
  • Chromosomes

 

16

What can be translocated in mutations? 

Chromosomes 

 

17

What kind of proteins are encoded for by oncogenes?

  • Growth factors
  • Growth factor receptors
  • Protein kinases/proteins that activate protein kinases
  • Proteins that control the cell cycle 
  • Proteins that affect apoptosis 
  • Transcription factors 

 

18

What do growth factors do? 

Stimulate cells to divide 

19

Give an example of a growth factor 

PDGF

20

What do growth factor receptors do? 

Transduce signals from the outside of the cell to the inside 

 

21

Give an example of a growth factor receptor

EGF receptor (erbB)

22

Give two examples of protein kinases

  • Src
  • Ras

 

23

Give an example of a protein that activates protein kinases

Raf

24

Give an example of a protein that controls the cell cycle

Cyclin D 

25

Give an example of a protein that affects apoptosis

Bcl-2 

26

Give an example of a transcription factor

Myc 

27

What is the significance of Myc in malignancy? 

It is one of the most commonly altered oncogenes 

28

What are the mechanisms of oncogene activation? 

  • Insertional mutagenesis
  • Chromosomal translocation
  • Chromosomal amplification
  • Point mutation
  • Ras signalling

29

What happens in insertional mutagenesis? 

DNA viruses incorporate a viral oncogene, which is inserted into the host DNA

30

Give two examples of viruses capable of insertional mutagenesis

  • Human papillomavirus 16/18
  • Hepatitis B

 

31

What is human papillomavirus 16/18 associated with? 

Cervical cancer 

32

What advancement has been made with HPV and cervical cancer? 

There is now an immunisation, so hopefully it will get eradicated over time

33

What is hepatitis B associated with? 

Hepatocellular cancer 

34

Give two examples of cancers caused by chromosomal translocations? 

  • Chronic myeloid leukaemia
  • Burkitt's lymphoma

 

35

What is the chromosomal translocation in chronic myeloid leukaemia? 

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

36

What is the result of the chromosomal translocation in chronic myeloid leukaemia? 

Fusion protein has abnormal tyrosine kinase activity 

37

What is chromosomal translocation in Burkitt's lymphoma?

8;14 - c-myc (8) is translocated onto igh (14) 

38

What is the result of the chromosomal translocation in Burkitt's lymphoma?

It produces a strong promoter leading to constitutive MYC expression

39

What happens in chromosomal amplification? 

Tumour genomic instability leads to amplification, and may lead to over-production of normal protein, as multiple copies of the same gene are being expressed

40

What can activate Ras?

Different activating mutations at codons 12, 13, and 61

41

What is the most commonly activated Ras oncogene? 

Ki-ras

42

How is Ras activated?

 By receptor tyrosine kinases that sit on the inside of the membrane

43

What kind of protein is Ras? 

A GTP-binding monomeric switch protein 

44

When is Ras active? 

When it is bound to GTP, and therefore inactive after GTP hydrolysis

45

What is the action of Ras? 

Activates the MAP kinase pathway

46

What does the type of Ras mutation determine in colorectal cancer? 

The prognosis 

47

What is the 2 year survival in colorectal cancer patients with mutant Ras compared to wild type Ras?

It is 49% in mutant ras, compared to 69% in wt ras

48

What mutations were significantly associated with a high risk of recurrence of colorectal cancer? 

12 TGT and 13 GAC

49

What did the RASCAL study find that the presence of KRAS mutation was associated with? 

An increased risk of recurrence and death 

50

How did the RASCAL II study results compare with RASCAL? 

It confimed the findings, but only in Dukes C (stage 3) tumours

51

What are the activating mutations in the RAS-MAPK, PI(3)K signalling network? 

  • KRAS
  • PI3KCA
  • BRAF

 

52

What do activating mutations in the RAS-MAPK, PI(3)K signalling network correlate with? 

Poor survival in colon cancers

53

What must the role of KRAS be interpreted in the context of? 

Other molecular and signalling abnormalities

54

What is any mutation in KRAS, BRAF, or PI3KCA associated with? 

A shorter 3 year survival

55

Where can a KRAS mutation status identify an increased risk of recurrence? 

In lymph nodes of stage 2 patients

56

Why is it difficult for pharmaceutical companies to block Ras? 

Ras is involved in widespread functions in the human body, but only 1 amino acid is changed in the mutant form, and so its hard to target. 

57

Give an example of a physiological role of Ras

It is an important pathway for synaptic remodelling in the human brain

58

What % of metastatic melanomas have a mutation in BRAF?

50%

59

What are the BRAF mutations found in metastatic melanoma?

Around 80% are V600E, 16% are V600K, and 3% are V600R

60

Are BRAF mutations found in benign nevi? 

Yes 

61

What is vemurafenib? 

A BRAF inhibitor developed by Plexicon and Genentech

62

What were the results of clinical trials involving vemurafenib? 

  1. In Phase I, 16 patients with stage 4 cancers were enrolled into the programme, and it increased median survival from 9 to 15 months
  2. In Phase II, 132 patients with stage 4 cancers were enrolled into the programme, and 53% of patients responded. 
  3. In phase III, 375 patients with stage III or IV cancers were enrolled in the programme, which compared vemurafenib to decarbazine. The trial was stopped early, and decarbazine patients were moved to vemurafenib

 

63

What is the problem with vemurafenib? 

It improves the patient for a window, but then the patient relapses with resistant disease

64

What gene is associated with human breast cancers? 

Her-2 (human epidermal growth factor receptor 2)

65

In what % of human breast cancers is her-2 amplified and over-expressed? 

10-30%

66

What is HER-2 amplification in breast cancer linked to? 

Poor prognosis - marker of aggressive cancer 

67

How is HER-2 amplification in human breast cancers detected? 

By FISH and immunohistochemistry 

68

How is HER-2 positive breast cancer treated?

With drugs that bind to the receptor and prevent growth

69

What drugs are used in the targeted therapy of HER-2 positive breast cancer?

  • Trastuzumab (Herceptin)
  • Pertuzumab (Perjeta)
  • Ado-trastuzumab emtansine (Kadcyla)
  • Lapatinib (Tykerb)

 

70

What kind of drug is herceptin? 

Monoclonal antibodies

71

What is herceptin often used with? 

Chemotherapy, but it can be used by itself 

72

What is herceptin used to treat? 

Early- and late-stage breast cancer 

73

How long would a patient typically take herceptin for after surgery? 

12 months

74

What kind of drug is perjeta?

Monoclonal antibody 

75

What can perjeta be given with? 

Trastuzumab and chemo 

76

When is perjeta given? 

Either before surgery to treat early-stage breast cancer, or to treat advanced trastuzumab in chemo 

77

What kind of drug is Kadcycla? 

A monoclonal antibody attached to a chemotherapy drug

78

What is kadcycla used to treat? 

Advanced breast cancer in women who have already been treated with trastuzumab and chemo 

79

What kind of drug is Tykerb? 

A kinase inhibitor 

80

What is tykerb used to treat? 

Advanced breast cancer, most often when trastuzumab is no longer working 

81

What is tykerb typically used with? 

Certain chemotherapy or hormone therapy drugs