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PMCOL 344 Cancer Exam Latest Update
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PMCOL 344 Cancer Exam LatestUpdate
Nucleobases - Answer Purine analogs that are converted into fake nucleotides that get
incorporated into DNA and inhibit various enzymes.
Camptothecin - Answer Topoisomerase 1B inhibitor that forms a stable tertiary complex
with TI-DNA complex. Causes DNA strand breaks that result in apoptosis. However, low
blood solubility.
Irinotecan - Answer Semisynthetic analogue of camptothecin to improve solubility while
retaining cytotoxicity. Topoisomerase 1B inhibitor that forms a stable tertiary complex
with TI-DNA complex. Causes DNA strand breaks that result in apoptosis. Prodrug that
is converted to its active form by carboxyl esterase. Inactivated by UGT1A1 and
CYP3A4.
FOLFIRI - Answer 5-fluorouracil, leucovorin, irinotecan -> for colon cancer.
Topotecan - Answer Semisynthetic analogue of camptothecin to improve solubility while
retaining cytotoxicity. Topoisomerase 1B inhibitor that forms a stable tertiary complex
with TI-DNA complex. Causes DNA strand breaks that result in apoptosis.
Rubicins - ALL (adriamycin) - Answer Anthracyclin - inhibits TI II (subtype independent)
and causes DNA strand breaks. Intercalative binding to DNA which partially unwinds
DNA (but tightly packed DNA not sensitive to this). Cell cycle non-specific. Formation of
free radicals (DNA strand breaks and cell membrane damage). Dose limiting
myelosuppression and mucositis (GI). Also cardiac toxicity but mechanism is delayed +
cumulative over life.
Dexrazoxone - Answer TI II inhibitor that reduced adverse cardiac effects in women on
Rubicins -> iron chelator (antioxidant), usually co-administered with carvedilol
(adrenoreceptor blocker) which is an antioxidant in cardiac tissue.
Mitoxantron - Answer Anthraquinone that acts like anthracyclines but with fewer
toxicities.
Pixantrone - Answer Anthraquinone that acts like anthracyclines but with fewer
toxicities.
Etoposide - Answer Podophyllotoxin derivative, non-intercalating inhibitor of TI II, forms
a stable tertiary complex with TI II-DNA, causes ss and ds breaks. Specific to late S and
early G2 phase. Dose limiting myelosuppression.
Teniposide - Answer Podophyllotoxin derivative, non-intercalating inhibitor of TI II,
, forms a stable tertiary complex with TI II-DNA, causes ss and ds breaks. Specific to late
S and early G2 phase. Dose limiting myelosuppression. Better cell accumulation than
etoposide.
Vincristine (CHO) - Answer Vinca alkaloids - binds to tubulin at the end of MTS and
dimers, prevents assembly of MTs (destabilizes) and causes dissolution of mitotic
spindles, inhibits organelle transport (esp in mitochondria of neural cells). Specific to
G1/S phase. Dose limiting peripheral neuropathy.
Vinblastine (CH3) - Answer Vinca alkaloids - binds to tubulin at the end of MTS and
dimers, prevents assembly of MTs (destabilizes) and causes dissolution of mitotic
spindles, inhibits organelle transport (esp in mitochondria of neural cells). Specific to
G1/S phase. Dose limiting myelosuppression.
Paclitaxel - Answer Taxol, binds to tubulin and enhances its polymerization (stabilizer),
inhibits cell replication and is specific to G2/M phase.
Docetaxel - Answer Taxol, binds to tubulin and enhances its polymerization (stabilizer),
inhibits cell replication and is specific to G2/M phase. Higher affinity for tubulin binding
site than paclitaxel. Dose limiting myelosuppression. Can cause hypersensitivity r
reactions.
Noscapine - Answer Isoquinoline alkaloid that agonizes sigma opioid receptor. Can be
used as a non-sedating antitussive but is being investigated for cancers bc fewer side
effects than other MT disruptors. Also a poor substrate for efflux transporters.
Tamoxifen - Answer SERM (for cancer). Competitive inhibitor of ER in breast tissue
(used in ER+ and PR+ breast cancer), prophylactic treatment for high risk ppl. Prodrug
metabolized by CYP2D6. Side effects include hot flashes, endometrial cancer (due to
agonistic effects one receptors in the uterus), thromboembolic events, depression.
SSRIs interfere with CYP2D6 activity and reduces effectiveness.
Raloxifen - Answer SERM (for cancer). Competitive inhibitor of ER in breast tissue and in
the uterus. Agonist effects in bone to treat osteoporosis in menopausal women. Only
effective in ER+ cancers.
Anastrazole - Answer Second-line hormonal therapy for breast cancer, selective
aromatase inhibitor so can't produce estrogen.
Leuprolide - Answer Medical castration - GnRH agonist that essentially desensitizes
pituitary so it stops releasing LHRH, decreasing T production. Initial T flare before
sensitization.
Degarelix - Answer GnRH antagonist for prostate cancer. Decreases T production, no
flare.
Abiraterone - Answer Androgen synthesis inhibitor. Inhibits CYP17A1 (so prevents
production of pregnenolone and progesterone to their 17-a derivatives, and the
formation of DHEA and androstenedione!). Used in castration-resistant prostate cancer.
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