Diffuse intrinsic pontine glioma, or DIPG, is a particularly deadly type of brain tumor that occurs in childhood and was first identified over forty years ago. This form of cancer has a 1% survival rate over five years. Since its discovery, researchers have devoted an incredible amount of effort to the development of chemotherapy for DIPG. However, it is only recently that improved research has begun making headway in the fight against this tumor.
The History of DIPG Research
Diffuse intrinsic pontine glioma can be defined by the keywords in its name. Pontine glioma refers to the location of the tumor – within the glial cells of the pons, which is a part of the brainstem and controls vital functions like breathing, balance, and sleep. Pressure from a DIPG tumor can put a patient at severe risk by limiting these functions. As a diffuse tumor, DIPG grows into the other tissues surrounding it and is poorly contained, making surgical removal nearly impossible without damaging the brain.
Due to its deadly nature, researchers have undertaken over 200 different clinical trials in an effort to combat the tumor via chemotherapy. Some of these chemotherapy drugs have even proven highly successful in diminishing other cancers and were once considered likely candidates for DIPG treatment. Unfortunately, most of these previous trials have failed.
Larger Scale, Larger Scope
Recently, Michelle Monje, MD, PhD – a pediatric oncologist at Stanford University, began a partnership with the National Institute of Health to pursue a different avenue for finding a DIPG treatment. Through the use of high-throughput screening methods, Michelle’s team has been able to make significant advances in understanding DIPG.
Instead of performing clinical research on single chemotherapy drugs, Monje’s team aims to isolate a combination of two drugs that can work together to combat the growth of the tumor. The hope was that two drugs could succeed where other individual drugs have failed.
However, the nature of this method requires researchers to perform multiple tests on nearly 3,000 approved and experimental drugs for the first phase of the trial. Monje’s team tested each individual drug on six lines of DIPG samples in order to identify the drugs with the most potential to positively affect the tumor. From the seven million potential combinations, researchers chose nearly 9,000 pairs for final testing.
High-Throughput Screening Leads to Hope
Monje’s team analyzed over 20,000 individual data points throughout the course of this study. Under traditional circumstances, such extensive testing would have taken a considerable amount of time. However, the use of high-throughput screening methods allowed researchers to analyze tens of thousands of samples per day, resulting in the production of data sets for comparison much more quickly.
Two drugs, panobinostat and marizomib, emerged as a pairing that has the potential to aid in the fight against DIPG. Both drugs work individually to interfere with the cancer’s ability to produce nicotinamide adenine dinucleotide, a key component in cell metabolism. Together, these drugs have the potential to prevent DIPG’s metabolism while leaving healthy cells untouched.
While this method is not a cure, preventing DIPG metabolism is an important step forward in a multi-tiered approach to treating this tumor. Michelle Monje’s use of high-throughput screening has proven the advantages of the ability to test such large quantities of samples at a time. In the future, her methods and current knowledge regarding DIPG and other cancers will continue to provide advances in chemotherapy for difficult cancers.