Anti-neoplastic Agents Flashcards
Regarding the cell cycle, activation of oncogenes overrides with checkpoint? What about inactivation of tumor suppressors; what checkpoint in overidden? Where are majority of cells (and tumor cells)?
- G1 arrest
- G2 Arrest
- G0 (just higher proportion of tumor cells growing faster than others)
The p53 tumor suppressor is associated with which checkpoint?
G2
The proportion of tumor cells that are not in G0 are referred to as _. This is the proportion [responsive/unresponsive] to chemotherapeutics.
Tumor cell growth fraction
Responsive
The presumed ultimate cause of lethality following cancer are _. These are [responsive/unresponsive] to chemotherapeutics. Why are they hard to detect?
Micrometastases
Responsive
Below the level of detection
The two examples of bischlorethamines (alkylating agents) provided are _. Which is the orally bioavailable and less reactive version that requires activation in target tissues or in the liver?
Mechlorethamine and Cyclophosphamide
Cyclophosphamide
What is the mechanism of action of the bischlorethamines?
Cause the formation of cross-linked guanine residues in DNA, leading to cell death (necrosis?)
As a class of alkylating agents, a major characteristic of nitrosoureas compared to others is _. This makes them particularly suitable for tumors located in _.
They cross the BBB
CNS tumors
Procarbazine is an alkylating agent that metabolized to _. As with other alkylating agents, its mechanism if action is _
Free radical intermediates (reactive)
Cross linking DNA to cause damage
Nitrosoureas and procarbazine are profoundly cross reactive with other antineoplastic agents. True or false?
False. Both groups non-cross reactive
A major risk with the use of procarbazine is _
It is leukemogenic, especially worse than the other alkylating agents
Methotrexate is an antitumor antimetabolite. It is an analog to _. Its works by targeting _ enzyme, preventing the synthesis of DNA, RNA and proteins
Folic acid Dihydrofolate reductase (converts dihydrofolate to tetrahydrofolate)
Methotrexate accumulates in cells as a _ derivative. It is specific to _ phase of the cell cycle.
Polyglutamate derivative
S (synthesis) phase
To rescue a cell from the toxic effects of methotrexate, _ can be given at the same time
Folinic acid (Leukovorin)
What are 4 mechanisms by which methotrexate resistance can occur in cells?
Increased DHFR expression
DHFR mutation
Reduced methotrexate uptake
Increase methotrexate efflux
The 2 purine antagonists provided as examples are _. They work by inhibiting _.
6 mercaptopurine , 6 thioguanine
denovo purine synthesis
Purine antagonists function during what phase of the cell cycle?
S (synthesis) phase
What is the enzyme required for the activation of 6 mercaptopurine and 6 thioguanine? What is the effect of a mutation or downregulation of this enzyme?
hypoxanthine-guanine phosphoribosyl
transferase (HGPRT)
Cell resistance to the drugs
How is xanthine oxidase related to the administration of 6 mercaptopurine? What is a very common source of xanthine oxidase?
Xanthine oxidase inactivates 6 mercaptopurine
Cow’s milk
What is a common drug coadminstered with 6 mercaptopurine to inhibit the enzyme xanthine oxidase? How does this affect the needed dose of 6-mercaptopurine?
Allopurinol
Need to reduce the dose of 6 mercaptopurine
5FU (flurouracil) is a pyrimidine antagonist that is metabolized into _, which inhibits the enzyme _. Inhibition of said enzyme results in _
fluorodeoxyuridine monophosphate (FdUMP) Thymidylate synthetase Thymineless death (no thymine made)
A pyrimidine antagonist, 5FU is active in what phase of the cell cycle?
S (synthesis) phase
What is capecitabine? What are 2 types of cancers that it is used for?
A prodrug of 5FU
Colon cancer, refractory breast cancer
What is the major enzyme that metabolizes capecitabine to 5FU? This enzyme might preferentially activate this drug in tumor tissues
Thymidine phosphorylase
What is the metabolite of cytarabine (araC) that is an inhibitor of DNA synthesis? What class of drug does cytarabine belong to? How does it exert its functions?
araCTP
Pyrimidine antagonists
it incorporates and terminates the DNA strand
