Anticancer Therapy

Question 1

Cyclin D

Answer 1

Triggered by growth factors

Promotes G0 -> G1 transition which eventually leads to mitosis

Question 2

DNA Damage = Kill Cell

Answer 2

Damage causes acute metabolic reaction involving PARP = ligation of DNA strands (Uses NAD)

Excessive damage = loss of NAD = Use ATP to regenerate = ATP depletion = lose homeostasis = necrosis

Question 3

Methotrexate

Answer 3

Inhibits Dihydrofolate Reductase = necessary for methyl transfer to dUMP to make TMP = inhibition of DNA synthesis and purine synthesis

Resembles folate

Myelosuppression toxicity

Question 4

5-fluorouracil

Answer 4

Metabolized into FdUMP = inhibits Thymidylate synthase = decrease thymidine monophosphate = decrease DNA synthesis

Question 5

Vincristine

Answer 5

Mitotic spindle poison -> binds to tubulin dimers and dissolves mitotic spindle = cell division inhibited

Toxicity = myelosuppression

Question 6

Paclitaxel (taxol)

Answer 6

Binds tubulin and ihibits disassembly of tubulin in microtubules = microtubules cant function to segregate chromosomes in M phase = aapoptosis

Toxicity = myelosuppression

Question 7

Etoposide (Vp-16)

Answer 7

Stabilizes covalent complex between topoisomerases and DNA = blockage of religation of DNA after strand passage = single strand break

If replication enzymes encounter this complex = irreversible double strand break

Toxicity = myelosuppression

Question 8

Ways to cause DNA damage

Answer 8

Radiation = Ionizing, photodynamic w/ drug (ROS generation = PARP and p53)

Covalent modification of DNA by drug (PARP and p53)

DNA strand breaking agent

Anthracyclines = DNA damage

Topoisomerase inhibition

Question 9

Anthracyclines

Answer 9

Intercalate in between bases of DNA

Induce reactive oxygen species that damage DNA

Inhibit topoisomerase

PARP and p53

Question 10

Anthracyclines Toxicity

Answer 10

Myelosuppresive

Cardiac toxicity = cardiomyopathy after chronic treatment