Tests for assessing p53 activity in tumor suppression versus DNA damage responses

Stanford investigators have found a mechanistic difference between p53's ability to induce responses to acute DNA damage (either apoptosis or cell cycle arrest) versus oncogenic stimuli. In other words, p53 variants can be active tumor suppressors but have a weak or null response to DNA damage. Compounds that inhibit p53's DNA-damage response without affecting its tumor suppression activity are desirable because p53-induced apoptosis due to DNA damaging chemotherapies and radiation therapies causes unnecessary side effects of these therapies

The researchers have developed a collection of mouse models that, in combination, can be used to screen for compounds that inactivate p53-triggered apoptosis due to DNA damage but not p53's tumor suppression activity.

In addition, the investigators have identified different gene expression signatures downstream of p53 in tumor suppression and DNA damage-induced apoptosis. These are the first known signatures to determine whether p53's tumor suppression activity is functional.