Nonspecific Cancer Chemotherapy Flashcards
(38 cards)
Typically, cancer is treat with ______ drugs
Numerous drug combinations
What are chemotherapy protocols based on?
The specific cancer (type) AND how far along it is (stage)
the PRIMARY tumor dictates chemotherapy
T/F chemo protocols are evidence based
True
What is a phase dependent drug?
The drug only works in one phase of mitosis
- S and M are the 2 most important phases to kill rapidly dividing cells
- S = copying DNA
- M = cell splitting
- Stop cell in either of these phases = cell death
What is a non-phase dependent drug?
Highly destructive drugs that work at any given time (stage doesn’t matter)
What is non-specific chemotherapy?
Chemotherapy will kill cancer cells but also normal cells
- Kills any dividing cell
- Inhibits the cell’s ability to copy DNA and or block mitosis
- Can be phase dependent OR non-phase dependent
What is targeted chemotherapy?
Chemotherapy will kill only cancer cells because of some component that makes them different from normal cells
-Blocks enzymatic pathways or inhibits growth factor binding to key receptors
What are two important targets of non-specific chemo?
- DNA (damage cell DNA –> cell can’t copy and replicate)
- Mitotic tubules (cells can’t pull apart –> no division)
What are the advantages of non-specific phase independent chemo?
- Kill everything at anytime (including resting G0)
- Very effective at killing
What are the disadvantages of non-specific phase independent chemo?
- HIGHLY toxic
- Kill anything including normal resting cells
- Numerous adverse effects
How do phase independent drugs do damage?
- They bind to and attack DNA
- They are able to cross-bind to two bases on the DNA 2bl helix
- *They break the integrity of the DNA helix and then DNA cannot copy = no cell division = cell death
What are the two types of phase independent drugs?
- Alkylating agents
- Platinum compounds
- They both bind to and attack DNA
What bases in the DNA helix do the drugs bind to?
Guanine bases
What type of bond is created between the DNA helix and the platinum/alkylating agent?
Covalent Bond (very strong bond --> irreversible) -Whatever it binds to WILL die
What two things are required for DNA synthesis?
- Four bases (A,G,T,C)
- FOLATE
What do S phase (non-specific phase dependent) inhibitors specifically inhibit?
Either: -Folate metabolism -Purine bases (A/G) -Pyrimidine bases (T/C) (OVERALL they inhibit DNA synthesis)
What enzyme is folic acid a co-factor for?
Dihyrdofolate reductase (widely used enzyme in a number of synthetic pathways)
What is dihyrdofolate reductase essential for?
The conversion of uracil to thymidine
-Thymidine = necessary base to make DNA
What happens if the interaction between folic acid and dihydrofolate reductase is inhibited?
Thymidine won’t be produced and then DNA can’t be made and cell will die
What is methotrexate?
A false folic acid (folate analogue)
- Looks like folic acid
- Enzyme brings this drug into the active site but it isn’t folic acid so the enzyme isn’t activated and thymidine isn’t produced and DNA isn’t synthesized
- Never should be used in pregnancy
What is the antidote to methotrexate?
Folic Acid
Can you reverse the action of methotreaxte?
Yes, because it is bound with Hydrogen binds (weak bonds) so if you give pt an influx of folic acid it can kick methotrexate out of the active site
What are S phase anti-metabolites?
“fake” DNA bases (nucleotides)
How do S phase anti-metabolites work?
They are recognized by DNA polymerase as a base but once they’re in the DNA binding site, DNA polymerase shuts down and DNA cannot be synthesized
