The most frequently mutated gene across all types of cancers is a gene called p53 (image shows 3-D structure of p53 protein). Unfortunately, it has been difficult to directly target this gene with drugs. Now a multi-institutional research team, led by Dr. Lewis Cantley and investigators at Weill Cornell Medical College, has identified a family of enzymes they say is crucial for the growth of cancers that have genetic aberrations in p53. Targeting these enzymes with novel agents might prevent the growth of p53 mutant cancers, thereby benefiting a broad spectrum of cancer patients, including those with breast, ovarian, lung, colorectal, and brain tumors. In the November 7, 2013 issue of Cell, investigators pinpoint two cellular enzymes -- Type 2 phosphatidylinositol-5-phosphate 4-kinases α and β (Type 2 PIP kinases) -- as essential for cancer growth when cells have lost p53, the powerful tumor-suppressor gene long dubbed the "guardian of the genome." More than half of all cancers lose this gene, allowing these cancers to grow at will. The researchers discovered that the Type 2 PIP kinases are not critical for the growth of normal cells but become essential for cell growth when p53 is lost due to mutations or deletions. The scientists showed, in animal and lab studies of human cancer cells, that targeting these molecules effectively shuts down the growth of p53 mutant cancers. Although the studies were conducted in human breast cancer cells, the researchers believe Type 2 PIP kinase inhibitors could block the growth of various cancers with a mutated or missing p53 gene. "The fact that one can delete the Type 2 PIP kinases in normal human cells or in mice with essentially no effect on cell survival suggests that inhibitors of these enzymes should have little toxicity," says Dr.Login Or Register To Read Full Story