The p53 gene (also referred to as tumor protein 53, TP53) is known as a tumor suppressing gene, as it codes for a protein that inhibits the development and growth of tumors. However, if the gene becomes altered or mutated, these mutations begin a series of events that leads to a loss of control of cell growth and proliferation. In other words, damaged cells are allowed to survive, and ultimately, develop into cancer cells.
Traditional cancer treatments have been largely unfocused as they indiscriminately kill dividing cells, cancer or otherwise, which often leads to significant toxic side effects in patients. Conversely, targeted therapies try to inhibit one or more abnormal proteins that are found in proliferating cancer cells thus resulting in programmed cell death.
P53 mutations have not historically been targeted by existing cancer treatment options, however, due to the gene’s central importance in many human cancers, restoring function to mutated p53 proteins has been described as one of the three holy grails of cancer research. Targeting specific abnormal proteins such as p53 found only in cancer cells is also expected to be associated with less toxicity in normal healthy cells.
Mutations of the p53 gene are the most common genetic alterations in human cancers, occurring in:
- More than 50% of all human cancers;
- Approximately 96% of ovarian cancers;
- Approximately 50% of non-small cell lung cancers;
- Between 40-50% of colorectal cancers; and,
- A wide range of other cancers, including breast, liver, bladder, pancreatic, esophagus and bone cancers.