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.Pharmacology > Part 8: Cancer Treatment 2 > Flashcards

Part 8: Cancer Treatment 2 Flashcards

1
Q

what 4 new things have newer antineoplastic agents been ab;e to target?

A
  1. new blood vessel growth (angiogenesis)
  2. growth and proliferation
  3. survival proteins
  4. hormone sensitive growth
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2
Q

what are survival proteins?

A

cancer cells have them to help ignore cell death signals

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3
Q

how can hormone supression help slow cancer?

A

some cancers grow in response to hormones

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4
Q

tyrosine kinase receptors are involved in ____ signalling in cancer cells

A

proliferative

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5
Q

receptor tyrosine kinases have ___ monomer subunits that transverse the cell membrane

A

2

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6
Q

what happpens to a tyrosine kinase receptor when a ligand binds?

A

subunits dimerize and intracellular domains phosphorylate each other, starting th esignalling cascade

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7
Q

intracellular tyrosine kinase (not membrane spanning) initiate _____ with the cell

A

downstream signalling responses

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8
Q

what sort of signals ae being sent by tyrosine kinases in cancer cells?

A

proliferative and survival

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9
Q

how are tyrosine kinase inhibitors used to fight cancer?

A

inhibit the tyrosine kinases that are sending the prolifereative and survival signals to cancer cells

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10
Q

what are 3 ways to inhibit tyrosine kinase with drugs?

A
  1. bind the circulating ligand
  2. block the receptor
  3. prevent receptor activation by blocking phosphorylation
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11
Q

the ____ receptor is a receptor tyrosine kinase involved in angiogenesis

A

VEGF

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12
Q

if blood supply to the tumour is impaired, what happens to the tumour?

A

growth is impaired

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13
Q

what does VEGF stand for?

A

vascular endothelial growth factor

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14
Q

what is the purpose of ant-VEGF treatment?

A

limit angiogenesis and stunt cancer tumour growth

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15
Q

VEGF are part of the _____ class of tyrosine kinase receptors

A

transmembrane

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16
Q

what is the first approach to reduce the effects of VEGF?

A

reduce the amount of VEGF circulating

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17
Q

what is Bevacizumab?

A

monoclonal antibody that targets VEGF

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18
Q

how is Bevacizumab used in cancer treatment?

A

monoclonal antibodies are designed to target a specific epitope, in this case it binds to VEGF and prevents it from binding to the VEGF receptor

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19
Q

what is the secon approach to reduce the effects of VEGF ?

A

prevent activation of the VEGF signalling pathway

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20
Q

how are small molecule tyrosine inhibitors like sorafenib used in cancer treatment?

A

bind to th eintracellular part of the VEGF receptor and prevent autophosphorylation, inhibiting signalling pathways

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21
Q

what is the epidermal grwoth factor receptor and its involvemnet in cancer?

A

receptor tyrosine kinase, a hormone that stimulates growth and proliferation of cells

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22
Q

one type of EGF, the HER-2 receptor is significantly upregulated in ____- cancer

A

breast

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23
Q

what is trastuzumab and its role in cancer treatment?

A

monoclonal antibody that binds to the extracellular domain of the HER-2 receptor, preventing binding of EGF to the tumour cells , reducing growth

24
Q

trastuzumab is a first line treatment for what type of cancers?

A

breast

25
Q

binding of trastuzumab to HER-2 also flags the cell for ___

A

destruction by the immune system

26
Q

what is the normal function of our endogenous antibodies?

A

flag foreign particles and cells to be recognized by immune cells to be cleasred from the body

27
Q

monoclonal antibodies require ____ administration

A

parenteral

28
Q

monoclonal antibodies have a very ____ half life. How often should treatment with a mab be given?

A

long; once every few weeks

29
Q

what is BCL-2?

A

a pro-survival protein shown to be upregulated in cancer

30
Q

how does BCL-2 prevent apoptosis?

A

stabilizes the mitochondria

31
Q

BCL-2 can be upregulated in cancer cells by increasing the signalling of _____

A

BCR-ABL

32
Q

what is BCR-ABL?

A

a cytosolic tyrosine kinase

33
Q

how is BCR-ABL activated?

A

kinase domain is the enzyme active site, where intercaction with a substrate causes phosphorylation and initiates the signalling cascade that upregulates BCL-2

34
Q

what happens if the activity of BCR_ABL is blocked by a small tyrosine kinase inhibitor?

A

prevents initiation of the signalling pathway that upregulates BCL-2

35
Q

what is the role of imatinib in cancer treatment?

A

small tyrosine kinase that inhibits signalling of BCR-ABL

36
Q

imatinib blocks the ____ tyrosine kinase, BCR-ABL

A

cytosolic

37
Q

why is it important that imatinib and sorafenib are small?

A

need to exert their effects within the cell, so their size and lipophillic character helps them cross the membrane

38
Q

what is a disadvantage of the small size of imatinib and sorfenib?

A

makes them good substrates for membrane transporters such as efflux pumps, which can result in tumour resistance to the drugs

39
Q

are all tumours that originate in hormone responsive tissues hormone sensitive?

A

no

40
Q

how are tumours tested to see if they are hormone sensitive>?

A

removed, stained to see if hormone receptors are upregulated

41
Q

what are some common cancers that can be hormone sensitive?

A

ovarian, breast, testicular

42
Q

breast cancer cells that lack estrogen, progesterone, and HER-2 receptors are called ___

A

triple negative breast cancers

43
Q

are triple negative breast cancers easier or harder to treat?

A

harder, bc fewer druggable targets

44
Q

normally, estrogen is produced in the ___ in response to secretion of hormones from the ___ and ___

A

ovaries; hypothalamus, pituitary gland

45
Q

estrogen receptors are ___ receptors that interact with ____ elements on DNA when activated to influence gene ____ and modulate cellular processes such as proliferation

A

intracellular; gene response elements; transcription

46
Q

what is the role of tamoxifen in cancer treatment?

A

estrogen receptor antagonist used for estrogen + cancer treatment by blocking the proliferative signals of estrogen

47
Q

tamoxifen is a _____ (competive/non-competitive) estrogen receptor antagonist

A

competitive

48
Q

what types of cancer is tamoxifen used in?

A

breast and sometimes ovarian

49
Q

what is the first choice drug fro estroge + cancers?

A

tamoxifen

50
Q

t/f in many cancer treatments a combo of drugs are used to try and increase efficacy

A

t

51
Q

what are 3 reasons combo cancer treatment is a good idea?

A
  1. increase efficacy
  2. reduce drug specific ADRs
  3. reduce drug specific resistance
52
Q

when using a combo treatment, do you use drugs of the same of different MOA?

A

different

53
Q

t/f in many cases cancer combos involve both older and newer anti-cancer agents

A

t

54
Q

most combinations are chosen based on ____ for specifc cancers

A

clinical trial data

55
Q

example of a 3 drug combo used in lung cancer

A

CAV (cyclophosphamide, adriamycin (doxorubicin) , vincristine)

56
Q

example of a combo therapy used in breast cancer

A

ACTT (adriamycin (doxorubicin), cyclophosphamide, taxol (paciltaxel), and trastuzumab)

.Pharmacology (55 decks)

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