New Discoveries About DIPG

Recent research has produced new discoveries about diffuse intrinsic pontine glioma (DIPG). For example, it has been found that parenchymal metastasis and leptomeningeal dissemination are more common in DIPG than previously believed.

Testing of tumor samples has shown there are a number of substantial genetic and epigenetic alterations. One of the most significant of such alterations is a type of histone mutation (specifically H3.3K27M), which is present in 70 to 80 percent of DIPG tumors and is associated with poor outcomes of these patients. The H3.3K27M mutation leads to global decrease of H3K27 di- and trimethylation, but increased H3K27 methylation at some other site, leading to altered expression of a large number of genes. The significance of this mutation has led to the new category (diffuse midline glioma H3 K27M–mutant) in the WHO classification of CNS tumors. (See news item about this finding.) Other significant mutations include those genes that regulate cell growth, such as PDGF receptors and TP53.

Both types of these new discoveries are helping doctors and scientists understand the tumor better, and new therapies are being designed based on these findings. These new therapies are being tested in the labs and in early-stage clinical trials.

New Therapies Under Study for DIPG

A number of new therapies and strategies are being studied for DIPG:

Repeat radiation therapy. Various regimens to deliver repeat radiation therapy to DIPG patients have been studied over the last few decades for their effectiveness. Repeat radiation therapy is increasingly accepted as the standard treatment for DIPG at relapse. This therapy is continually being studied and improved.

Strategies to improve drug delivery to the tumor. The blood-brain barrier (BBB), with its critical function of keeping blood-borne toxins out of the brain, also prevents most drugs from reaching the brain tumor. There are a number of strategies to overcome the BBB, including bypassing it. Convection-enhanced delivery (CED) is the main method under study for this strategy. In CED, a catheter or catheters are inserted into the tumor, and the drug is slowing infused directly into the tumor. (See video below this paragraph.) Another strategy is to open the BBB for drug delivery, using either certain chemical agents (such as adenosine) or physical energy (such as ultrasound). Intra-arterial delivery also improves drug delivery to brain tumors, and is often used in conjunction with chemical opening of the BBB.

Therapeutic vaccines. In therapeutic vaccines, immune cells are stimulated with tumor material to fight cancer cells. There are a number of therapeutic vaccines under study for DIPG, utilizing different choices of tumor material and immune cells. Some vaccines utilize an individualized approach and some don’t.

Modulating immune response. This has long been a strategy under study for cancer treatment. PD-1 checkpoint therapy has seen great success recently in the treatment of lymphoma, melanoma, and some other cancers. However, a recent clinical study of an antibody against PD-1 in DIPG patients produced a high rate of serious adverse events. This signifies that further improvement is needed for this strategy in the treatment of DIPG.

Drug therapies utilizing tumor-specific or tumor-related mutations. Some of the mutations found in DIPG are targetable with available therapeutic agents, and such therapeutic regimens are being tested in the labs and in early-stage clinical trials. This includes epigenetic modifying agents (such as panobinostat) and agents acting on receptor tyrosine kinases (such as crenolanib). The use of these therapeutic agents may be combined with strategies to improve drug delivery in brain tumors.

The above is not an exhaustive list of strategies under study for DIPG therapy. There are a number of clinical trials (more than 40 in the United States alone) for DIPG. Learn about our CED clinical trial at Memorial Sloan Kettering Cancer Center, or reach out to our experts on DIPG by calling Dr. Souweidane's office at 212-746-2363.


Reviewed by: Mark Souweidane, MD
Last reviewed/last updated: April 2022

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