LEcture 12- Cancer chronotherapies

Question 1

what drugs are metions in this stidy

Answer 1

camptothecins- 5-fu
platinum compounds- oxiplatin
Irinotecan

Question 2

5-FU

Answer 2

detoxified by DPYD which is higher at rest

Question 3

Oxiplatin

Answer 3

forms DNA adducts-cell death

detoxified by GSH which has a lower toxicity at activty hours

Question 4

Irinotecan

Answer 4

bioactivated by CES2
SN38/TOP1/DNA complex
detoxified and exported by ABC transporters

Question 5

Circadian relevance of irnotecan`

SEX

Answer 5

best tolerance (7-15)
expression of ABC transporters are rythmic, more seen during a peak 12 activity hours(in mice)
SEX dependance expression
females express transporters later than male mice

bioactivation
export

Question 6

Chronotheraphy

Answer 6

Deregulated locks in tumours- shield healthy cells
women need to be optimised
chronotheraphy of oxiplatin-5-fu-lv increase survival rates in metastatic colorectal cancer