Research

Cancer Cells Can Eat Themselves: Using Autophagy in Research

by St. Baldrick's Foundation
May 10, 2012


By St. Baldrick’s Fellow, Don Coulter, M.D.

Despite advancements in pediatric oncology research, the outcome of children with high-risk neuroblastoma hasn’t progressed much throughout the years, compared to the rate of progress in diseases like leukemia. In fact, even with current treatments, over half of the patients with high-risk neuroblastoma still succumb to the disease with long-term survival rates at only about 30% – 50%.

These staggering statistics led me to focus on high-risk neuroblastoma for my research. I wanted to find new treatments that can help make an impact on childhood cancer survival rates. Over the years, researchers have been looking for more innovative ways of reading neuroblastoma cancer cells. My study focuses on an interesting cellular process called autophagy to treat neuroblastoma.

The meaning of autophagy is in the word itself: auto- means self and -phage is a Latin term for eating. It’s a way for the cells to eat themselves, which all cells do. The process of autophagy is similar to a farmer – if there’s a good amount of sun and rain, a farmer’s crops will grow, enabling him to expand his farm. However, if there’s a drought, then the farmer is going to have to depend on what he’s saved in his barn to feed his family. Cancer cells act the same way. If there’s not a lot of nutrition, cancer cells will shrink down, eat their own parts and sometimes die.

As one of St. Baldrick’s first fellows, I started my research looking at different agents that not only have the capacity to kill cancer cells, but also induce autophagy to get at them from two different ways. My team and I examined two types of drugs, rapamycin and valproic acid, that were already approved for children and had the possibility of destroying cancer cells.

One of the substances that neuroblastoma tumor cells produce that can make them very harmful is a protein called N-MYC. N-MYC causes the cancer to grow rapidly. However, when we treated the neuroblastoma cancer cells with the drug rapamycin, we observed that the cells not only decreased production of the N-MYC protein, but it also triggered the cells to start the process of destroying it.

The other medicine we looked at, valproic acid, is a drug that’s been approved for children a long time ago to help with seizures. We used this medicine because it can make those cells go into autophagy. Our lab tested this combination of drugs on human neuroblastoma cells in petri dishes and found that these agents had an impact on the way that the cancer cells grew, and the way that they were able to produce the protein, N-MYC.

After just completing a phase I trial with the drug combination of rapamycin and valproic acid, the next step of our research hopefully will include a phase II trial, where we will carefully observe how these two drugs really affect cancer in children with high-risk neuroblastoma. Thanks to the funding from the St. Baldrick’s Foundation, our team will soon be able to move our research from the lab, or bench, to the bedside, where we can improve patient care and treatment for kids with cancer.

Read about how St. Baldrick’s is training the next generation of childhood cancer researchers like Dr. Coulter.


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