Friday, November 8, 2013

New Study Provides Hope for Treatment of Cancers with p53 Mutations

P53 is the most frequently mutated gene across all types of cancers. However, directly targeting this vital protein with drugs has been difficult. A report in the current issue of Cell entitled: 'Depletion of a Putatively Druggable Class of Phosphatidylinositol Kinases Inhibits Growth of p53-Null Tumors' describes the work of a multi-institutional collaboration that has identified potentially important enzymes that are essential for growth of cancers where p53 is mutated but not critical for the growth of normal cells. By targeting these enzymes it is hoped that a broad group of cancer patients will see benefits including those with breast, lung and brain tumors.

Cartoon representation of a complex between
DNA and the protein p53

by Thomas Splettstoesser

The enzymes in question are called Type 2 phosphatidylinositol-5-phosphate 4-kinases alpha and beta (Type 2 PIP kinases). The scientists knew that one of the critical roles of p53 is to 'rescue' cells which are producing too much reactive oxygen species (ROS) which is a by-product of rapid growth. In the absence of p53 excessive ROS can cause further DNA damage and cancer growth can become even more aggressive. However, too much ROS will cause excessive damage to cellular components and eventually death of the cell. Type 2 PIP kinases appear to be a backup to p53 and reduce ROS enough to keep the cells from dying. The research described in the current paper employed breast cancer cells which were known to have higher expression of Type 2 PIP kinases. They found that genetically targeting these enzymes effectively shuts down the growth of these cancer cells and these scientists believe that the results will extend to other cancers with mutated p53.

The search now begins for drugs that target Type 2 PIP kinases using appropriate inhibitor screening technology like the HTS capable PHERAstar FS microplate reader from BMG LABTECH.