cancer resis

Question 1

alkylating agents

Answer 1

enzymes inactivate the drugs inside the cells
ie CYP450, conjugation by glutathione S transferases

overexpressed in tumour cells

Question 2

target modification

Answer 2

to topoisomerase II
against etoposide

modified topoisomerases

Question 3

increases in DNA repair pathway

Answer 3

nitrosourea resistant cells - produce high levels of akyltransferases to repair guanine lesion and prevent crosslinking

Question 4

cisplatin

Answer 4

histone remodelling - overexpression of HATs
ie Tip60 in resistant lung cancer

impair imvolves MMR and NER
ERCC play main role in NER so is upregulated in ovarian cancer cells

Question 5

altered gene expression resistance

Answer 5

ie loss of p53
loss of induction of apoptosis
cell cyle progression starts
loss of DSB repair coordinator

Question 6

methotrexate resistance
metabolic bypass
prevent uptake

Answer 6

methotrexate resistance

by upregulating DHFR ( metabolic bypass)

mutation in folate carrier - reduce affinity for methotrexate but able to still carry folate.

Question 7

multidrug transporter efflux pumps

vinca alkaloids
anthracyclines
mitoxantrones

Answer 7

P glycoprotein MDR1 ( ABCB1)

multidrug resistance associated proteins - MRP1, 2 aka ABCC1,2

breast cancer resistant protein ABCG2