anti-cancer: drug resistance

Question 1

mechanisms of resistance to anti cancer drugs - mnemonic

Answer 1

“my specific resistance gives big tits”,
metabolism
specificity
DNA repair
gene expression
bypass (metabolic)
transporters/efflux pathways

Question 2

drug metabolism

Answer 2

based on CYP450 and conjugation by glutathione S-transferase etc

Question 3

specificity changes

Answer 3

• resistance to etoposides
• have modified topoisomerases

Question 4

DNA repair

Answer 4

1. nitrosourea-resistant cells: alkyltransferases that repair G lesions so prevent cross-linking
2. cisplatin: more DNA repair enzymes

Question 5

altered gene expression

Answer 5

won’t enter mitotic pathway if lose p53

Question 6

metabolic bypass

Answer 6

methotrexate resistance;
- more DHFR
- less uptake because carrier mutated so less affinity

Question 7

enhanced drug efflux

Answer 7

multi drug transporters e.g.
- P-glycoproteins MDR1 (ABCB1)
- multidrug resistance-associated proteins (MRP1 & 2, also ABCC1 & 2)
- breast cancer resistance protein (ABCG2)

e.g. against vinca alkaloids, anthracyclines, mitoxantrone