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Updated: Aug 3, 2025
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Therapeutic avenues for targeting treatment challenges of diffuse midline gliomas
Aleeha Noon1, Stefanie Galban2
1College of Medicine, California Northstate University, 9700 W Taron Drive, Elk Grove, CA 95757, USA.
Abstract:
Diffuse midline glioma (DMG) is the leading cause of brain tumor-related deaths in children. DMG typically presents with variable neurologic symptoms between ages 3 and 10. Currently, radiation remains the standard therapy for DMG to halt progression and reduce tumor bulk to minimize symptoms. However, tumors recur in almost 100% of patients and thus, DMG is still considered an incurable cancer with a median survival of 9-12 months. Surgery is generally contraindicated due to the delicate organization of the brainstem, where DMG is located. Despite extensive research efforts, no chemotherapeutic agents, immune therapies, or molecularly targeted therapies have been approved to provide survival benefit. Furthermore, the efficacy of therapies is limited by poor blood-brain barrier penetration and inherent resistance mechanisms of the tumor. However, novel drug delivery approaches, along with recent advances in molecularly targeted therapies and immunotherapies, have advanced to clinical trials and may provide viable future treatment options for DMG patients. This review seeks to evaluate current therapeutics at the preclinical stage and those that have advanced to clinical trials and to discuss the challenges of drug delivery and inherent resistance to these therapies.
Insights
Diffuse midline glioma (DMG) is a deadly pediatric brain cancer. Current treatments are insufficient, but novel drug delivery and targeted therapies show promise for future DMG treatment.
Area of Science:
- Pediatric neuro-oncology
- Brain tumor research
- Cancer therapeutics
Background:
- Diffuse midline glioma (DMG) is the primary cause of pediatric brain tumor mortality.
- DMG presents with neurological symptoms in children aged 3-10, with a poor prognosis and median survival of 9-12 months.
- Standard radiation therapy is insufficient, with nearly all tumors recurring, and surgery is often contraindicated due to tumor location.
Approach:
- This review evaluates preclinical and clinical trial therapeutics for DMG.
- It examines challenges in drug delivery, including blood-brain barrier penetration.
- The review also discusses inherent tumor resistance mechanisms impacting treatment efficacy.
Key Points:
- No chemotherapeutic, immune, or targeted therapies are currently approved for DMG with survival benefits.
- Existing therapies face limitations due to poor blood-brain barrier penetration and tumor resistance.
- Novel drug delivery systems and emerging targeted/immunotherapies are advancing to clinical trials.
Conclusions:
- Despite significant challenges, ongoing research into novel drug delivery and targeted therapies offers hope for improved DMG treatment outcomes.
- Further investigation into overcoming drug resistance and enhancing blood-brain barrier penetration is critical.
- Clinical trials of advanced therapies may provide future viable options for pediatric DMG patients.
