Anti Cancer Flashcards
what are the two types of classical cytotoxic therapies?
- radiotherapy and photodynamic therapy
2. chemotherapy
what are the 4 types of chemotherapy?
- antimetabolites
- agents disrupting critical target proteins
- DNA damaging agents
- agents that work by combo of cytotoxic mechanisms
what are the 5 antimetabolites associated with chemotherapy?
- folic acid antagonist
- DNA base analogs
- ribonucleotide reductase inhibitor
- protein synthesis inhibitors
- proteasome inhibitors
what are the two agents that disrupt critical target proteins?
- topoisomerase inhibitors
- mitotic spindle proteins
what are the three DNA damaging agents?
- covalent modifiers of DNA
- DNA strand breaking agents
- DNA intercalators
what are the only agents that work by a combo of cytotoxic mechanisms
mutagenic antibiotics/anthracyclines
a major problem of development is drug resistance. during therapy, the resistant end of the distribution may survive and continue to evolve even stronger through_______
darwinian selection
cancer results when you ____ oncogenes or you _____ tumor suppressor cells
- activate
- inactivate
cells can be stimulated into the cycle for growth of cancer by growth factors that trigger an increase in ____
Cyclin D
______ starts the timed increases ion the other cyclins in order to prepare for and to carry out MITOSIS
cyclin D/CDK
cancer results from an imbalance between what?
cell growth and cell death
growth factor receptor ______ can stimulate MITOSIS via cyclin D
tyrosine kinase signaling
growth factor signaling can also do what?
- repress apoptosis
- promote cell survival
*these are things we don’t want to happen in cancer cells
anticancer drugs do what?
- inhibit mitosis
- cause necrosis (cell ruptures) or apoptosis (volume dec)
***we DO want these things to happen
receptor tyrosine kinase signaling can do what?
- stimulate mitosis by raising cyclin D which triggers cells to enter the cell cycle
- inhibit cell death
_____ act on steps of receptor tyrosine kinase signaling to sequester it
target agents
why is combination therapy good for fighting cancer?
it gives the cell two problems to deal with simultaneously making it harder to evolve two resistant traits at once. treatment should be given REPEATEDLY and it is good to use agents with different MECHANISMS and TOXICITIES
what is the goal of cytotoxic chemotherapy?
SELECTIVE TOXICITY
larger fractions of cancer cells are in mitosis and this can be exploited (using combination therapy)
the most common dose limiting side effect of cytotoxic chemotherapy is _______
myelosuppresion
this causes immunosupression (inc susceptibility to infection and cancers) as well as thrombocytopenia (inc bleeding time)
inhibiting topoisomerases involves what?
DNA twisting stress built up by enzymes running along the DNA double helix cannot be relieved. Supercoils prevent enzymes/polymerases from using the DNA. Cell may react by digesting DNA leading to DNA damage
if you inhibit micrtotubule function what happens?
chromosomes cannot segregate and cells cannot divide
methotrexate does what?
inhibits dihydrofolate reductase which results in a block of DNA synthesis by no synthesis of TMP
it also separately inhibits PURINE ring synthesis which reduces DNA and RNA synthesis (no proteins made)
does this all by MYELOSUPPRESSION
what does 5-fluorodeoxyuridine monophosphate (FdUMP) do?
inhibits thymidylate synthase —> dec TMP —> dec DNA synthesis
how does vincristine (oncovin) work?
it binds to tubulin dimers and inhibits tubule polymerization
*this polymerization was needed for chromosomes to separate in the M-phase leading to apoptosis
how does taxol work?
bind to tubulin (like vincristine) but instead it inhibits the disassembly of tubulin in microtubules
*the result is the same, microtubules cannot function to segregate chromosomes in the M phase leading to apoptosis
how does etoposide work?
-inhibitor of topoisomerase II
produces a single strand bread that is reversible until replication enzymes encounter it and an irreversible DOUBLE STRAND break results
what are covalent modifiers of DNA
- they covalently modify DNA
- the repair process may create DNA breaks that activate PARP and p53 as before, killing cells by necrosis and apoptosis, and inducing growth arrest
- may cause myelosuppression as a side effect
*very similar to etoposides
three mechanisms of anthracyclines
- intercalation in DNA - inhibition of DNA and RNA synthesis, mutagenesis (done by polymerases)
- generation of free radicals : P450 –> O2 goes to superoxide –> DNA strand scission –> PARP and p53 mediated cell death
- inhibitions of topoisomerases II: DNA breaks occur when replication enzymes encounter the complex
DNA damage may cause apoptosis and growth arrest by what?
inc p53
