Inactivation of PTEN allows tumours to resist radiation therapy

Researchers at Washington University School of Medicine in St. Louis have shown that tumours with PTEN mutations are often resistant to radiation therapy. The PTEN gene produces a protein found in almost all tissues in the body. This protein prevents cells to grow and divide too rapidly. Prostate cancer, endometrial cancer, melanoma and some brain tumours have as a similarity these mutations in PTEN.

Tej K. Pandita, Ph.D., a researcher with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital, and his colleagues want to know how a common genetic mutation makes cancer radiation resistant.

Cells pass through several phases as they grow and divide, each phase having its own checkpoints that assess whether a cell is healthy enough to continue with these two procedures. If the situation is perceived otherwise, signals from checkpoints should predict future steps to be taken, either repairing or death.

Pandita, associate professor of radiation oncology and of genetics, said “The defective checkpoints contribute to radioresistance. When a cell gets damaged by radiation, normally checkpoints will make it stop growing to repair the damage. If the checkpoints are working but the cell has a defective DNA repair system, the cell will be radiosensitive. But if the checkpoints don’t operate, the cell can bypass DNA repair and continue to grow and divide. Then the cells are radioresistant.”

In order for the tumours with PTEN mutations to increase radiation sensitivity, there will be needed further development of drugs that could correct the faulty checkpoints. This is a subject for further studies as the work continues.

This research was supported by Funding from National Institutes of Health.