Biomedical Engineering Reference
In-Depth Information
0.010
0.005
0.000
-0.005
-0.010
-0.015
-5
0
5
10
15
20
25
30
time (days)
Fig. 5
Daily mean growth rates for cancer (
solid line
) and healthy cells (
dashed line
) when starting
drug infusion at time 0. After a 10-day transient phase, the drug-forced biological system stabilizes
towards the expected asymptotic growth rate
problem to an age-structured model accounting for three phases of the cell cycle,
G
1
,
S
G
2
and
M
. As a first step in our analysis, we preferred keeping the model as
simple as possible, in the absence of actual knowledge of the duration of
M
phase,
but taking it as fixed, for instance to 1 h, such considerations might be developed in
future works to assume that we have, thanks to FUCCI reporters, accessed the main
two checkpoints,
G
1
/
/
S
and
G
2
/
M
.
8
Future Prospects: Multi-target Multi-drug Delivery
Optimisation in Physiologically Structured Cell Population
Models
From a therapeutic point of view, we have only represented the action of one drug
acting on cell cycle phase transitions (on only one transition,
G
2
/
M
, if it acts on
S
phase). We know indeed that, in particular via p53, drugs that create DNA damage
ultimately act by blocking the cell cycle at checkpoints, mainly
G
1
/
M
,and
this only subsequently sends the cell into apoptosis, therefore cell cycle transition
checkpoints are the most accurate targets to represent the effect of most cytotoxic
drugs. The action of spindle poisons, such as taxans and vinca alcaloids, that block
the cell cycle in
M
phase (but not at
G
1
/
S
and
G
2
/
S
or
G
2
/
M
), might also be represented by
using the same formalism.
Search WWH ::
Custom Search