Part 8: Cancer Treatment 2 Flashcards
what 4 new things have newer antineoplastic agents been ab;e to target?
- new blood vessel growth (angiogenesis)
- growth and proliferation
- survival proteins
- hormone sensitive growth
what are survival proteins?
cancer cells have them to help ignore cell death signals
how can hormone supression help slow cancer?
some cancers grow in response to hormones
tyrosine kinase receptors are involved in ____ signalling in cancer cells
proliferative
receptor tyrosine kinases have ___ monomer subunits that transverse the cell membrane
2
what happpens to a tyrosine kinase receptor when a ligand binds?
subunits dimerize and intracellular domains phosphorylate each other, starting th esignalling cascade
intracellular tyrosine kinase (not membrane spanning) initiate _____ with the cell
downstream signalling responses
what sort of signals ae being sent by tyrosine kinases in cancer cells?
proliferative and survival
how are tyrosine kinase inhibitors used to fight cancer?
inhibit the tyrosine kinases that are sending the prolifereative and survival signals to cancer cells
what are 3 ways to inhibit tyrosine kinase with drugs?
- bind the circulating ligand
- block the receptor
- prevent receptor activation by blocking phosphorylation
the ____ receptor is a receptor tyrosine kinase involved in angiogenesis
VEGF
if blood supply to the tumour is impaired, what happens to the tumour?
growth is impaired
what does VEGF stand for?
vascular endothelial growth factor
what is the purpose of ant-VEGF treatment?
limit angiogenesis and stunt cancer tumour growth
VEGF are part of the _____ class of tyrosine kinase receptors
transmembrane
what is the first approach to reduce the effects of VEGF?
reduce the amount of VEGF circulating
what is Bevacizumab?
monoclonal antibody that targets VEGF
how is Bevacizumab used in cancer treatment?
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
what is the secon approach to reduce the effects of VEGF ?
prevent activation of the VEGF signalling pathway
how are small molecule tyrosine inhibitors like sorafenib used in cancer treatment?
bind to th eintracellular part of the VEGF receptor and prevent autophosphorylation, inhibiting signalling pathways
what is the epidermal grwoth factor receptor and its involvemnet in cancer?
receptor tyrosine kinase, a hormone that stimulates growth and proliferation of cells
one type of EGF, the HER-2 receptor is significantly upregulated in ____- cancer
breast
what is trastuzumab and its role in cancer treatment?
monoclonal antibody that binds to the extracellular domain of the HER-2 receptor, preventing binding of EGF to the tumour cells , reducing growth
trastuzumab is a first line treatment for what type of cancers?
breast
binding of trastuzumab to HER-2 also flags the cell for ___
destruction by the immune system
what is the normal function of our endogenous antibodies?
flag foreign particles and cells to be recognized by immune cells to be cleasred from the body
monoclonal antibodies require ____ administration
parenteral
monoclonal antibodies have a very ____ half life. How often should treatment with a mab be given?
long; once every few weeks
what is BCL-2?
a pro-survival protein shown to be upregulated in cancer
how does BCL-2 prevent apoptosis?
stabilizes the mitochondria
BCL-2 can be upregulated in cancer cells by increasing the signalling of _____
BCR-ABL
what is BCR-ABL?
a cytosolic tyrosine kinase
how is BCR-ABL activated?
kinase domain is the enzyme active site, where intercaction with a substrate causes phosphorylation and initiates the signalling cascade that upregulates BCL-2
what happens if the activity of BCR_ABL is blocked by a small tyrosine kinase inhibitor?
prevents initiation of the signalling pathway that upregulates BCL-2
what is the role of imatinib in cancer treatment?
small tyrosine kinase that inhibits signalling of BCR-ABL
imatinib blocks the ____ tyrosine kinase, BCR-ABL
cytosolic
why is it important that imatinib and sorafenib are small?
need to exert their effects within the cell, so their size and lipophillic character helps them cross the membrane
what is a disadvantage of the small size of imatinib and sorfenib?
makes them good substrates for membrane transporters such as efflux pumps, which can result in tumour resistance to the drugs
are all tumours that originate in hormone responsive tissues hormone sensitive?
no
how are tumours tested to see if they are hormone sensitive>?
removed, stained to see if hormone receptors are upregulated
what are some common cancers that can be hormone sensitive?
ovarian, breast, testicular
breast cancer cells that lack estrogen, progesterone, and HER-2 receptors are called ___
triple negative breast cancers
are triple negative breast cancers easier or harder to treat?
harder, bc fewer druggable targets
normally, estrogen is produced in the ___ in response to secretion of hormones from the ___ and ___
ovaries; hypothalamus, pituitary gland
estrogen receptors are ___ receptors that interact with ____ elements on DNA when activated to influence gene ____ and modulate cellular processes such as proliferation
intracellular; gene response elements; transcription
what is the role of tamoxifen in cancer treatment?
estrogen receptor antagonist used for estrogen + cancer treatment by blocking the proliferative signals of estrogen
tamoxifen is a _____ (competive/non-competitive) estrogen receptor antagonist
competitive
what types of cancer is tamoxifen used in?
breast and sometimes ovarian
what is the first choice drug fro estroge + cancers?
tamoxifen
t/f in many cancer treatments a combo of drugs are used to try and increase efficacy
t
what are 3 reasons combo cancer treatment is a good idea?
- increase efficacy
- reduce drug specific ADRs
- reduce drug specific resistance
when using a combo treatment, do you use drugs of the same of different MOA?
different
t/f in many cases cancer combos involve both older and newer anti-cancer agents
t
most combinations are chosen based on ____ for specifc cancers
clinical trial data
example of a 3 drug combo used in lung cancer
CAV (cyclophosphamide, adriamycin (doxorubicin) , vincristine)
example of a combo therapy used in breast cancer
ACTT (adriamycin (doxorubicin), cyclophosphamide, taxol (paciltaxel), and trastuzumab)
