Meningioma Mommas has awarded a $29,042 grant to University of Colorado researchers, Dr. Kevin Lillehei, Dr. Michael Graner, Dr. Philip Tatman and their support team (Team Colorado!) to continue their focus on, “Pre-clinical trial evaluation of HDAC inhibitors for the treatment of meningiomas.”
Meningiomas are a common primary brain tumor, accounting for 36% of all primary brain tumors. Their prevalence is 8.14 persons per 100,000; however, some autopsy reports have indicated their prevalence could be as high as 8.2% in the population . In spite of this high burden of disease, no FDA approved therapies exist for the treatment of meningiomas.
The need for additional treatments has become clear since the World Health Organization revision of the meningioma classification in 2007. This classification scheme has resulted in an increase in the number of tumors being classified as grade II, with some reports indicating grade II meningiomas may account for as many as 30% of all meningiomas. We have shown that 3-5% of grade I meningiomas do recur within five years and have an ability to resist treatment; as well as over 50% of grade II meningiomas and 90-100% of grade III meningiomas recur within five years. Considering these aggressive tumors collectively account for close to 38% (30% are grade II, 3% are grade III, and 5% are recurrent grade I) of all meningiomas, more research is needed to combat this highly under-studied neoplasm.
One possible approach to treatment is to attempt to repurpose existing therapies for the treatment of meningiomas. This approach has successfully identified effective therapies in numerous cancers, but relies heavily on the accuracy of the technology used to identify the compounds. Over the last year, our collaborative group, funded by Meningioma Mommas, developed such a platform that is capable of growing and culturing all meningiomas.
This platform allows us to grow and screen every meningioma resected at our institution. Moreover, whenever we receive more than 200 mgs of tissue, we are able to complete the full process within 10 days times. We typically get more than 200 mgs of tissue for ~84.7% of all tumors. For meningiomas specifically, 100% of the tumors we have received since starting this study have been over 200 mgs. This means we could potentially treat all meningioma patients on an individual basis, pioneering the way for personalized medicine.
So far, we have been screening meningiomas with two different compound libraries, one is an FDA approved library maintained by the National Cancer Institute, and the other is an epigenetic inhibitor library from Caymen Chemical.
Rather than focusing on the best possible treatments for each individual patient, we can also analyze the data to reveal any treatments that may be efficacious for all meningiomas.
In this proposal, we will evaluate the efficacy of targeting HDACs for the treatment of meningiomas. We will accomplish this in two aims, the first aim will be directed at verifying the efficacy of targeting HDACs using a series of knockout experiments in patient derived meningiomas tumor cell cultures, and the second will be a preliminary in vivo experiment to verify HDAC inhibitors can in fact efficaciously treat meningiomas in a Patient Derived Xenograft (PDX) mouse model.
Identifying HDACs as possible targets for the treatment of meningiomas has huge implications for treating these tumors. Our institution is currently part of a national multi-center clinical trial mechanism that allows us to immediately start clinical trials across 14 centers in North America as soon as we demonstrate efficacy of a drug for a specific tumor. The way this trial works, is that pharmaceutical companies offer compounds for use in the trial (currently, we have 84 available). If a researcher shows efficacy of one of these compounds in both in vitro and two independent in vivo models, a trail will be immediately started.
Team Colorado was previously awarded $29,443 to fund their project, “Determining the Therapeutic Potential of Targeting DNA Methylation in Meningiomas, and the Establishment of Aggressive and Recurrent Cell Lines.”
“We have developed a high throughput drug screen that has the potential to bring about an era of personalized medicine for all brain tumors. It just so happens that every meningioma we have screened shows high sensitivity to a specific class epigenetic inhibitors, suggesting meningiomas could be effectively treated with a single class of compounds that are already FDA approved. Our future work entails transitioning the drug screening platform from a proof of concept into a clinical tool, with the intention of revolutionizing our treatment approach to brain tumors. For meningiomas, we will work towards generating the data necessary to start a clinical trial using the identified novel class of epigenetic inhibitors. All of these findings are a direct result of the grant we received from Meningioma Mommas in May of 2018, less than one year ago! With their continued support, we will make great strides towards completing our vital work to relieve the physical and emotional burden carried by those suffering from meningiomas and other brain tumors.”
Meningioma Mommas is proud of its collaboration with locally-based researchers dedicated to improving the lives of meningioma patients.