A study funded by the National Cancer Institute, the National Institutes of Health, a Theodore N. Law Endowment for Scientific Achievement, and a Dodie P. Hawn Fellowship in Cancer Genetics Research surprisingly showed that the presence of normal p53, a tumor suppressor gene and not the mutated gene, was making chemotherapy with doxorubicin less effective in breast cancer; it is the mutated gene that actually enhances the benefit of the drug and not the reverse. This study moves us a step closer to personalized medicine for breast cancer.
“It’s really important to understand the genetic defects a tumor cell has before we treat it,” says lead investigator Guillermina Lozano, PhD, Professor and Chair, Department of Genetics at M.D. Anderson. “What we learned here is the complete opposite of what we expected. We thought tumors would respond better to treatment if the p53 gene was normal. But the opposite was true.” The study showed that the nonmutated p53 gene stopped cell division, resulting in cell aging, which allows cells to survive, thus fueling relapse. By contrast, the mutated p53 gene cells proceed into cell division with broken chromosomes caused by the chemotherapy, which is “a signal for the cell to die,” according to Dr Lozano.
The tumor suppressor p53 is mutated or inactivated in the majority of cancers, and approximately one third of breast cancers have this mutation. It has long been thought that normal p53 results in a better response to chemotherapy. “The response rates were mixed, and we never understood the difference. Now we understand that we need to know the p53 status to predict a response,” Dr Lozano stated. M.D. Anderson, news release, June 11, 2012.
