Illustration of brain tumor cells resisting treatment due to the blood-brain barrier.

Decoding Brain Tumors: How New Research Could Improve Glioblastoma Treatment

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Rhea Morgan in Health & Wellness August 2025 • 5 min read.

"Exploring Innovative Approaches to Target Glioblastoma Stem Cells and Overcome Drug Resistance"


Glioblastoma (GBM) is one of the most aggressive and challenging cancers to treat. Despite medical advances, the prognosis for patients with GBM remains poor, with a median survival of just 12-15 months. A key reason for this is the presence of glioblastoma stem cells (TICs), which are resistant to current therapies and drive tumor growth and recurrence. Understanding how to target and eliminate these TICs is critical for developing more effective treatments.

Recent studies have focused on specific proteins and pathways that are essential for the survival and maintenance of GBM TICs. One such protein is Lysine-Specific Histone Demethylase 1 (LSD1), an epigenetic regulator involved in stem cell maintenance, cell proliferation, and tumor development. Inhibiting LSD1 could disrupt GBM TIC activity and potentially improve treatment outcomes.

Another major hurdle in GBM treatment is drug resistance. The blood-brain barrier (BBB), which protects the brain from harmful substances, also prevents many drugs from reaching tumor cells. Additionally, certain proteins, like ABCB1 and ABCG2, actively pump drugs out of brain cells, further reducing the effectiveness of chemotherapy. Overcoming these drug resistance mechanisms is essential for improving treatment efficacy.

Targeting Glioblastoma Stem Cells with LSD1 Inhibitors

Illustration of brain tumor cells resisting treatment due to the blood-brain barrier.

Researchers have found that LSD1 is upregulated in human GBM tissues and patient-derived TICs compared to normal brain cells, suggesting it plays a crucial role in GBM development. Targeting LSD1 with chemical inhibitors or genetic silencing techniques does not affect the viability or proliferation of GBM TICs directly, but it significantly reduces their stem cell frequency. This means that inhibiting LSD1 can reduce the number of cells capable of driving tumor growth and recurrence.

Furthermore, studies have shown that targeting LSD1 prolongs the survival of GBM patient-derived xenograft models, indicating its potential as a therapeutic strategy. RNA-sequencing and ChIP-sequencing analyses have identified potential mediators of LSD1's biological activity, including genes known to be important for GBM biology and stemness maintenance. These findings highlight the importance of LSD1 for GBM TIC maintenance and GBM formation.

  • LSD1 is highly expressed in GBM TICs compared to normal brain cells.
  • Inhibiting LSD1 reduces the stem cell frequency of GBM TICs, both in vitro and in vivo.
  • Targeting LSD1 prolongs survival in GBM xenograft models.
  • LSD1 inhibitors may offer a new therapeutic approach for GBM management.
While LSD1 inhibitors show promise, researchers are also exploring ways to overcome drug resistance at the blood-brain barrier. ABCB1 and ABCG2 are drug efflux transporters that limit the brain penetration of many anticancer drugs. Inhibiting these transporters could increase the amount of drug reaching tumor cells, improving treatment effectiveness. Strategies to bypass the BBB or develop drugs that are not affected by these transporters are also being investigated.

The Future of Glioblastoma Therapy

The studies discussed offer hope for improving glioblastoma treatment by targeting glioblastoma stem cells and overcoming drug resistance. LSD1 inhibitors show promise in reducing the stem cell frequency of GBM TICs and prolonging survival in preclinical models. Strategies to overcome the blood-brain barrier and inhibit drug efflux transporters could also improve the effectiveness of chemotherapy.

However, more research is needed to fully understand the mechanisms underlying these effects and to develop safe and effective therapies for human patients. Clinical trials are necessary to evaluate the efficacy of LSD1 inhibitors and BBB-modulating agents in GBM patients. Further research into the molecular characteristics of GBM and the role of the immune system is also warranted.

By combining these innovative approaches, researchers hope to develop more effective and personalized therapies for glioblastoma, ultimately improving the prognosis and quality of life for patients with this devastating disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What is Glioblastoma and why is it difficult to treat?

Glioblastoma (GBM) is a particularly aggressive form of cancer, and it's incredibly challenging to treat. The median survival for those diagnosed with GBM is unfortunately quite low, only 12-15 months. This is a result of several factors, including the presence of Glioblastoma Stem Cells (TICs) that are resistant to current therapies and drive tumor growth and recurrence. Current treatments often struggle to effectively target and eliminate these TICs, making GBM a formidable opponent.

2

Why are Glioblastoma Stem Cells (TICs) so important in the context of Glioblastoma?

Glioblastoma Stem Cells (TICs) are crucial because they are resistant to current therapies and are a key driver of tumor growth and recurrence in Glioblastoma (GBM). These cells possess properties that allow the tumor to regenerate and spread, making treatment incredibly difficult. Targeting and eliminating these cells is considered essential to developing more effective treatments for GBM. The survival and maintenance of GBM TICs are linked to specific proteins and pathways that researchers are working to understand and disrupt.

3

What is LSD1 and why is it a target for Glioblastoma treatment?

LSD1, or Lysine-Specific Histone Demethylase 1, is a protein that has emerged as a potential target for Glioblastoma (GBM) treatment. It's an epigenetic regulator involved in stem cell maintenance, cell proliferation, and tumor development. Studies have shown that LSD1 is upregulated in human GBM tissues and patient-derived TICs compared to normal brain cells. Inhibiting LSD1 reduces the stem cell frequency of GBM TICs and prolongs survival in preclinical models, suggesting it plays a critical role in GBM TIC maintenance and GBM formation. Researchers believe that targeting LSD1 with chemical inhibitors or genetic silencing techniques could improve treatment outcomes.

4

What is drug resistance, and why is it a problem in Glioblastoma treatment?

Drug resistance is a significant hurdle in the treatment of Glioblastoma (GBM). The blood-brain barrier (BBB), which protects the brain from harmful substances, also prevents many drugs from reaching tumor cells. Additionally, proteins like ABCB1 and ABCG2 actively pump drugs out of brain cells, further reducing the effectiveness of chemotherapy. Researchers are exploring strategies to overcome these mechanisms, such as inhibiting these transporters, bypassing the BBB, or developing drugs that are not affected by them, to increase the amount of drug reaching tumor cells and improve treatment efficacy.

5

What are the main goals of current research in Glioblastoma therapy?

Researchers are optimistic about improving Glioblastoma (GBM) treatment. They are focusing on two main areas: targeting Glioblastoma Stem Cells (TICs) and overcoming drug resistance. LSD1 inhibitors show promise in reducing the stem cell frequency of GBM TICs and potentially prolonging survival. Simultaneously, strategies to overcome the blood-brain barrier and inhibit drug efflux transporters are being investigated to improve the effectiveness of chemotherapy. These advancements offer hope for more effective therapies to improve patient outcomes.

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