Abstract:
p53, an anti-tumor protein, is a significant protein against cancer suppression. It is controlled
by its natural inhibitor, Mdm2 protein. Both p53 and Mdm2 protein exist in the form of a
mutual feedback loop so that proper function of p53 protein continues. In various tumors p53
protein is significantly inactivated. This is attributed to the hyper-active levels of its inhibitor.
A novel drug, nutlin-3a is used against Mdm2 protein to control its hyper-active level in order
to reactivate the function of p53 protein. By far, small molecules of drug nutlin-3a is used as
the most promising techniques to reactivate p53 protein. Cancer patients have a high risk of
drug-drug interactions (DDI) owing to their multi-dosing prescriptions, which leads them to
adverse effects.
In the presented work, we have aimed to investigate the effect of pharmacodynamical
interaction between two anti-cancer drugs, aspirin and nutlin-3a in the activation of p53
protein. For this purpose, the problem is defined in terms of control system and a ProportionalIntegral-Derivative (PID) controller and an H∞ controller is designed. The comparative
performance of both the controllers is analysed by comparing the simulation results achieved.
For deep understanding and better results, two different doses of aspirin are used, i.e. a low
and a high dose of aspirin.
The result achieved through In-Silico trails shows that the hyper-active level of Mdm2 protein
is regulated to the desired equilibrium position. However, using a high dose of aspirin acts as
input disturbance and leads to undesirable ov
