Continuing The Battle: Recent Insights in Diffuse Midline Glioma’s (DMG/DIPG)

Copper Chelation Therapy?

The goal of copper chelating therapy is to remove copper accumulated in tissues and prevent re-accumulation. This type of therapy is commonly used in pediatric Wilson’s Disease. As excess copper has been linked to epigenetic, kinase (or enzyme) and metabolic dysregulation in various cancers, there is a consensus that copper chelating therapy may simultaneously target mechanisms of DMG. Research presented at the 2024American Association for Cancer Research Annual Meeting shared insights into their investigation of patient datasets, in vitro DMG cell lines and in vivo DIPG models. The data shared indicated there is a higher level of expression of a gene that produces a protein called a copper chaperone in DMG patient samples compared to samples from patients without DMG.

Using a copper chelator (TEPA) to treat DMG cells, researchers also observed efficacy in both in vitro (via apoptosis and growth assays) and in vivo studies (increased survival), providing a promising basis for future investigation of copper chelators as a viable therapeutic strategy in patients with DMG.

New Therapeutic Targets?

TIM-3 (T cell immunoglobulin and mucin domain-3) is classified as an inhibitory immune checkpoint. It works to dampen or suppress immune responses. Interestingly, researchers in Spain have revealed TIM-3 as a promising new therapeutic target for the treatment of DMG. They also observed that TIM-3 was highly expressed in both tumour cells and immune cells in DIPG patient samples; and using mouse models, demonstrated that TIM-3 blockade prolonged survival, with 50% of long- term survivors being disease-free and acquiring immunological memory to prevent tumour recurrence. This pre-clinical data offered strong support for initiating a clinical trial with an anti-TIM-3 antibody for the treatment of DIPG as monotherapy or even with other already proven treatments (e.g., oncolytic viruses or CAR-T cells).

In another study, researchers from the U.S. focused on an enzyme known as extracellular-signal-related kinase 5 (ERK5) and the gene PFKFB3. ERK5 plays an important role in several cellular processes, such as cell proliferation and cell differentiation while PFKFB3 regulates glycolysis in tumour cells (extracting energy from glucose). Previous studies of DMG have shown that ERK5 is critical for tumour growth. Researchers showed that in vitro and mouse models of DMG are sensitive to the loss of PFKFB3 and therapies which jointly target the ERK5-PFKFB3 axis may represent a promising therapeutic approach in patients with pediatric DMG.

Relentless and Unyielding

In the realm of DMG, this latest research, amongst many others, provides relentless hope through pioneering thought. By defying conventional boundaries and collaborating on grand scales, scientists and clinicians areunyielding and building foundations that will lead to new and exciting discoveries in the years to come.

Disclaimer: Information in this article is sourced from published articles; readers are advised to independently verify facts. Opinions expressed are the author's own and do not necessarily reflect those of the publisher. If you or someone you know experience symptoms related to DMG, consult with a medical professional for personalised advice and guidance.

References

Abstract 525: A comprehensive approach: Copper chelation therapy modulates epigenetic, kinase signaling and metabolic pathways in diffuse midline gliomas (DMG) | Cancer Research |

American Association for Cancer Research (aacrjournals.org )

The rise of TIM‐3: A promising immune target in diffuse midline gliomas - PMC (nih.gov )

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma (cell.com )

Epigenetic and Metabolic Changes in Diffuse Intrinsic Pontine Glioma - PMC (nih.gov )