Anti Cancer

Question 1

what are the two types of classical cytotoxic therapies?

Answer 1

1. radiotherapy and photodynamic therapy

2. chemotherapy

Question 2

what are the 4 types of chemotherapy?

Answer 2

• antimetabolites
• agents disrupting critical target proteins
• DNA damaging agents
• agents that work by combo of cytotoxic mechanisms

Question 3

what are the 5 antimetabolites associated with chemotherapy?

Answer 3

• folic acid antagonist
• DNA base analogs
• ribonucleotide reductase inhibitor
• protein synthesis inhibitors
• proteasome inhibitors

Question 4

what are the two agents that disrupt critical target proteins?

Answer 4

• topoisomerase inhibitors

- mitotic spindle proteins

Question 5

what are the three DNA damaging agents?

Answer 5

• covalent modifiers of DNA
• DNA strand breaking agents
• DNA intercalators

Question 6

what are the only agents that work by a combo of cytotoxic mechanisms

Answer 6

mutagenic antibiotics/anthracyclines

Question 7

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_______

Answer 7

darwinian selection

Question 8

cancer results when you ____ oncogenes or you _____ tumor suppressor cells

Answer 8

• activate

- inactivate

Question 9

cells can be stimulated into the cycle for growth of cancer by growth factors that trigger an increase in ____

Answer 9

Cyclin D

Question 10

______ starts the timed increases ion the other cyclins in order to prepare for and to carry out MITOSIS

Answer 10

cyclin D/CDK

Question 11

cancer results from an imbalance between what?

Answer 11

cell growth and cell death

Question 12

growth factor receptor ______ can stimulate MITOSIS via cyclin D

Answer 12

tyrosine kinase signaling

Question 13

growth factor signaling can also do what?

Answer 13

• repress apoptosis
• promote cell survival

*these are things we don’t want to happen in cancer cells

Question 14

anticancer drugs do what?

Answer 14

• inhibit mitosis
• cause necrosis (cell ruptures) or apoptosis (volume dec)

***we DO want these things to happen

Question 15

receptor tyrosine kinase signaling can do what?

Answer 15

• stimulate mitosis by raising cyclin D which triggers cells to enter the cell cycle
• inhibit cell death

Question 16

_____ act on steps of receptor tyrosine kinase signaling to sequester it

Answer 16

target agents

Question 17

why is combination therapy good for fighting cancer?

Answer 17

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

Question 18

what is the goal of cytotoxic chemotherapy?

Answer 18

SELECTIVE TOXICITY

larger fractions of cancer cells are in mitosis and this can be exploited (using combination therapy)

Question 19

the most common dose limiting side effect of cytotoxic chemotherapy is _______

Answer 19

myelosuppresion

this causes immunosupression (inc susceptibility to infection and cancers) as well as thrombocytopenia (inc bleeding time)

Question 20

inhibiting topoisomerases involves what?

Answer 20

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

Question 21

if you inhibit micrtotubule function what happens?

Answer 21

chromosomes cannot segregate and cells cannot divide

Question 22

methotrexate does what?

Answer 22

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

Question 23

what does 5-fluorodeoxyuridine monophosphate (FdUMP) do?

Answer 23

inhibits thymidylate synthase —> dec TMP —> dec DNA synthesis

Question 24

how does vincristine (oncovin) work?

Answer 24

it binds to tubulin dimers and inhibits tubule polymerization

*this polymerization was needed for chromosomes to separate in the M-phase leading to apoptosis

Question 25

how does taxol work?

Answer 25

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

Question 26

how does etoposide work?

Answer 26

-inhibitor of topoisomerase II
produces a single strand bread that is reversible until replication enzymes encounter it and an irreversible DOUBLE STRAND break results

Question 27

what are covalent modifiers of DNA

Answer 27

• 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

Question 28

three mechanisms of anthracyclines

Answer 28

1. intercalation in DNA - inhibition of DNA and RNA synthesis, mutagenesis (done by polymerases)
2. generation of free radicals : P450 –> O2 goes to superoxide –> DNA strand scission –> PARP and p53 mediated cell death
3. inhibitions of topoisomerases II: DNA breaks occur when replication enzymes encounter the complex

Question 29

DNA damage may cause apoptosis and growth arrest by what?

Answer 29

inc p53