Decreasing the Side Effects of Radiation Therapy for Brain Cancer Treatment
By inhibiting a certain enzyme, researchers might be able to dramatically improve results and decrease the side effects of radiation therapy for cancer treatment. The enzyme, called telomerase, is found in 85 percent of cancerous cells but is not found in normal mature cells.
“Telomerase allows cancer cells to continue to replicate indefinitely. By inhibiting it, we could make radiation treatment more effective in lower doses," said Rachid Drissi, PhD, a researcher in the Division of Hematology / Oncology at Cincinnati Children’s Hospital Medical Center.
Normal cells stop multiplying when the ends of their chromosomes get too short — these end pieces, called telomeres, act like a cap on the DNA. Think of tape on a shoelace that keeps the threads from unraveling. “Usually, as telomeres get to a certain critically short length, the cell will stop dividing,” said Drissi. “This is a natural process of cellular aging.” But when telomerase is present, it allows the cell to continue to divide beyond this natural stopping point by maintaining telomere length.
A telomerase inhibitor combined with radiation therapy works like a one-two punch, because radiation therapy damages the DNA enough to make it stop replicating. The telomerase inhibitor makes cells stop replicating when their telomeres are worn down. Also, cells with short telomeres become much more sensitive to radiation.
Ongoing clinical trials in adults use a telomerase inhibitor to treat breast cancer and multiple myeloma in adults. Now Drissi is working with clinical researcher Maryam Fouladi, MD, MSc, and others in the Division of Hematology / Oncology to develop a pediatric clinical trial using telomerase inhibitors. As a first step to test the efficacy of these inhibitors, Drissi is also assessing telomere length and telomerase levels in tumors and blood from children with an aggressive form of brain tumor. The goal is to determine the role of telomerase in predicting patient outcome and response to therapy in this vulnerable patient population.
“Brain tumors are difficult to treat, and these patients face tough choices between curing the cancer and living with the effects of radiation,” said Drissi. “Working in a research institution that is part of a hospital gives you a sense of how important the lab work really is.”
