you probably already heard or read the sentence, 50% of all tumors harbor a p53 mutation, so in these tumors p53's function is disturbed by a mutation. In the other 50% p53's function is disturbed by other mechanisms, for example the over expression of MDM2. MDM2 is the main negative regulator of p53 and inhibits it's (antitumor) function and degrades it, so over expression leads to much lower levels op p53. Therefore the p53 pathway isn't activated (induction of cell cycle arrest, senescence, apoptosis,...) in response to stress signals possibly leading to malignant transformation. By inhibiting the interaction between MDM2 and p53, for example by Nutlin, p53 levels rise and the pathway is activated. It is also interesting in combination therapies, for example the effect of a chemotherapeutic that induces apoptosis true the activation of the p53 pathway could be enhanced when combined with MDM2-p53 inhibitors. Several companies are developing Nutlin like molecules and for example RG7112 is already in clinical trial, so there are a couple of major companies jumping on board :). I found this an interesting review with an overview of the current drugs targeting the p53 pathway. http://www.nature.com/nrd/journal/v13/n3/full/nrd4236.html

you probably already heard or read the sentence, 50% of all tumors harbor a p53 mutation, so in these tumors p53's function is disturbed by a mutation. In the other 50% p53's function is disturbed by other mechanisms, for example the over expression of MDM2. MDM2 is the main negative regulator of p53 and inhibits it's (antitumor) function and degrades it, so over expression leads to much lower levels op p53. Therefore the p53 pathway isn't activated (induction of cell cycle arrest, senescence, apoptosis,...) in response to stress signals possibly leading to malignant transformation. By inhibiting the interaction between MDM2 and p53, for example by Nutlin, p53 levels rise and the pathway is activated. It is also interesting in combination therapies, for example the effect of a chemotherapeutic that induces apoptosis true the activation of the p53 pathway could be enhanced when combined with MDM2-p53 inhibitors. Several companies are developing Nutlin like molecules and for example RG7112 is already in clinical trial, so there are a couple of major companies jumping on board :). I found this an interesting review with an overview of the current drugs targeting the p53 pathway. http://www.nature.com/nrd/journal/v13/n3/full/nrd4236.html

You may not be aware of the fact that many companies have been working on mdm2 since the 90s. One of the problems may be the fact that mdm2 is an unfavorable drug target (protein/protein interaction; multiple potential side effects)

The companies have been trying to target this pathway since long time ago, however the results are extremely disappointing. The interaction is difficult to target, there are problem of specificity and in addition this molecule would be beneficial only for p53 wt expressing tumours, which typically have lower aggressiveness, better sensitivity to standard therapy and better prognosis.