Understanding TP53 and the Role of Tumor Suppressor Genes in Cancer Development

For many years, scientists have understood that certain types of genetic mutations are at the origin of cancer. When functioning regularly, tumor suppressor genes can prevent the uncontrolled proliferation of malignant cells and trigger the process of apoptosis, a type of cell death. Tumor suppressor genes (protective genes) can become dysfunctional as a result of mutations, which could favor the growth of cancer, the study shows.

The suppressor gene called TP53 effectively “restricts” the development and growth of many different types of tumors in the human body and is the most commonly mutated tumor suppressor gene in human cancers. This gene encodes a protein called p53which is both a strong inhibitor of cell proliferation and an inducer of apoptosis.

“In more than half of cancers, TP53 is not mutated, instead remaining in a latent state. Consequently, many research efforts have been devoted to the development of drugs that could reactivate this latent form of p53 for cancer therapy. However, most cancers respond to p53 activation by these drugs with a transient block in cell proliferation. A better response to these drugs would be to eliminate the cancer cells by apoptosis. Therefore, it is critical for us to understand what other factors are required for an effective p53-targeting cancer therapy,” explains Zdenek Andrysik, PhD, research assistant professor of pharmacology at the University of Colorado School of Medicine and a among the authors of the paper.