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New drug shows promise in treating Ependymoma

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By Anthropic AI

 

Ependymoma is a type of rare brain tumor that occurs in the central nervous system. While surgery is often the main treatment, finding effective drug therapies has been challenging. However, new research is providing hope that an experimental drug may offer benefits for patients with recurrent or refractory ependymoma.

 

Breakthrough in Drug Development

A team of researchers from Memorial Sloan Kettering Cancer Center recently published results from an early phase clinical trial evaluating the drug entinostat in patients with recurrent ependymoma. Entinostat belongs to a class of drugs known as histone deacetylase (HDAC) inhibitors which works by modifying gene expression in cancer cells. In the study, 17 patients with recurrent intracranial ependymoma received oral entinostat daily for 21 days followed by a 7 day break, in repeated 28 day cycles. According to the researchers, the drug showed encouraging antitumor activity with 7 patients achieving stable disease for 6 months or more. No unexpected toxicities were observed however common side effects included fatigue, nausea, vomiting and anorexia. Based on these promising initial results, further studies of entinostat alone and in combination with other drugs are warranted to confirm its efficacy.

 

Mechanism of Action Offers New Approach

Ependymoma Drug works through a novel mechanism of action compared to standard chemotherapy drugs. It functions as an epigenetic regulator by inhibiting HDAC enzymes. This alters the acetylation of histone proteins leading to changes in gene expression within cancer cells. Specifically, entinostat causes the activation of tumor suppressor genes and induction of cellular senescence or programmed cell death (apoptosis). As ependymomas lack targeted therapies, HDAC inhibitors provide a rational new strategy by modifying gene expression to stop tumor growth. According to the study authors, entinostat represents the first clinical evidence that an HDAC inhibitor may benefit patients with refractory ependymoma. They noted further exploration of epigenetic therapies for this disease is highly justified.

 

Encouraging Results Warrant Larger Studies

While the findings are preliminary due to the small study size, experts say the results with entinostat are encouraging. According to Dr. Gregory Friedman, an oncologist at Memorial Sloan Kettering Cancer Center who was not involved in the study, "For a rare tumor like ependymoma which has limited treatment options after initial surgery and radiation, stable disease for 6 months or more is definitely meaningful. It suggests the drug may be controlling tumor growth beyond what we'd expect with standard therapies alone." He noted larger trials are still needed but the tolerable side effect profile coupled with signs of drug activity provide rationale to further evaluate entinostat's potential.

 

Dr. Daniela A. Bax, senior author of the study and pediatric neuro-oncologist at Memorial Sloan Kettering Cancer Center, expressed optimism over the results. She stated “This proof-of-concept study demonstrates entinostat's ability to induce anti-tumor effects in recurrent ependymoma patients and establishes the scientific rationale to further investigate epigenetic therapies for this disease. Our findings support continued exploration of entinostat alone and in rational combinations to maximize its benefit for ependymoma patients.” Based on these positive early findings, Dr. Bax's team is now planning a multi-institutional phase 2 trial of entinostat to confirm its efficacy

 

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