Pharmacology 33 (Intro To Cancer)

Front 1

carcinogenesis

Back 1

process that creates a stem cell line or clonogenic line of cells

Front 2

what is the importance of the growth fraction of tumor cells?

Back 2

in general, the higher the growth fraction, the better the cancer will respond to chemotherapy b/c cells in G0 are resistant to chemotherapy

Front 3

what is the average growth fraction of tumors?

Back 3

20%

Front 4

which phase of the cell cycle can vary significantly in malignant cells?

Back 4

G1

Front 5

cell cycle-specific chemotherapy agents

Back 5

high growth fraction necessary to be effective

Front 6

cell cycle-nonspecific chemotherapy agents

Back 6

kill in any phase (even G0), but work better on cycling cells

Front 7

what molecules normally sense DNA damage in cells?

Back 7

p53

arrests cell cycle to allow time for the damage to be repaired

if damage isn't repaired, apoptosis occurs

Front 8

how does chemotherapy work?

Back 8

damages DNA, causing p53 to sense the damage and arrest the cell cycle

in normal cells, the DNA will be repaired and the cell will recover

in cancer cells, DNA repair is defective, so the cell is driven to apoptosis

Front 9

what tissues have high growth fraction (aside from tumors)?

Back 9

(1) Bone marrow
(2) GI epithelium
(3) Hair follicles

Front 10

what causes inherent resistance of some cancer cells to chemotherapy drugs?

Back 10

heterogeneity

Front 11

what does it mean for a cancer to be "treatable"?

Back 11

treatment will be given infrequently to buy a small amount of time
(prolonged survival but with recurrence of Sxs btwn treatments and eventual death)

Front 12

what is the effect of chemotherapy drug combinations?

Back 12

tumor cell kill exceeds regrowth, drug resistance does not develop and "cure" results

Tx must be continued long after all clinical evidence of cancer have disappeared (1-3 years)

Front 13

what is the advantage of surgery with intensive adjuvant therapy to remove primary tumors?

Back 13

decreases the number of tumor cells present, so it decreases the chemotherapy necessary to eradicate the tumor cells

Front 14

what are the advantages to drug combinations in chemotherapy?

Back 14

(1) if dose-limiting toxicities vary, the drugs can be used at nearly full dosing
(2) different mechanisms of action potentially eradicate tumor subclones that are resistant to one or the other of the agents
(3) drugs can act with synergy (or at least with additive effects)

Front 15

what is the log-kill hypothesis?

Back 15

a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells

Front 16

primary cancer resistance

Back 16

little or no kill response to first treatment with chemotherapy

Front 17

acquired cancer resistance

Back 17

decrease in kill response that occurs 2-3 years after chemotherapy is initiated

resistant subclones of tumor cells are selected for by initial treatments

Front 18

P-glycoprotein

Back 18

ATP-dependent pump of anti-cancer drugs from the cell

often responsible for multidrug resistance

pumps out chemo agents like vincristine, vinblastine, doxorubicin, bleomycin, etoposide, and others

Front 19

what are the purines?

Back 19

adenine
guanine

both used in DNA and RNA

Front 20

what are the pyrimidines?

Back 20

cytosine (DNA and RNA)
uracil (RNA only)
thymine (DNA only)

Front 21

what are the derivatives of purines and pyrimidines?

Back 21

ribonucleosides (base attached to ribose)
ribonucleotides (base attached to ribose, with phosphate attached to ribose)
deoxyribonucleosides (base attached to deoxyribose)
deoxyribonucleotides (base attached to deoxyribose which is attached to phosphate)

Front 22

what enzyme is responsible for catalyzing the reduction of ribonucleotides to deoxyribonucleotides?

Back 22

ribonucleotide reductase

Front 23

what is folate used for?

Back 23

1-carbon transfer reactions to make DNA, RNA, and proteins

Front 24

what is required to make inosine monophosphate (IMP)?

Back 24

amino acids
phosphoribosylpyrophosphate
folate

Front 25

what is the purpose of inosine monophosphate (IMP)?

Back 25

aminated to adeylate (AMP)
oxidized to guanylate (GMP)

these ribonucleotides are then reduced to deoxyribonucleotides which are then used for DNA synthesis

Front 26

how is deoxythymidine monophosphate synthesized?

Back 26

PRPP and Amino Acids form orotate, which then forms uridylate monophosphate, which is then converted to deoxyuridylate monophosphate and is finally converted to deoxythymidine monophosphate with a carbon donated from folate

Front 27

what is the common thread between all alkylating agents?

Back 27

they are all capable of reacting in a manner such that an alkyl group or a substituted alkyl group becomes covalently linked to cellular constituents

Front 28

what are the alkylating agents?

Back 28

cyclophosphamide
mechlorethamine
chlorambucil
melphalan
carmustine
lomustine
semustine
bendamustine

Front 29

what are the chemotherapy agents in the MOPP regimen?

Back 29

M - mechlorethamine
O - oncovin (trade name for vincristine)
P - procarbazine
P - prednisone

Front 30

what alkylating agents require metabolism to a reactive compound?

Back 30

cyclophosphamide
procarbazine

Front 31

what is the most useful alkylating agent?

Back 31

cyclophosphamide