“From the bottom of my heart, I sincerely thank Meningioma Mommas for supporting our
research. In a time when research funding is so competitive, any penny counts!
“Fearless” is the spirit that I have learned from patients with meningiomas like you.
Despite how many tumors and surgeries you have and how life-altering the effects of
these tumors are, you “never give up!” I strongly believe that with your dedication and
support, one day we will be able to eliminate this debilitating disease.
The overarching goal of our research is to develop a medical therapy that effectively
eradicates both NF2-associated and sporadic meningiomas. To achieve this objective,
we have undertaken two approaches. First, as the NF2 gene, which encodes tumor
suppressor Merlin, is frequently inactivated in these tumors, we have interrogated two
novel antibodies that target specific receptor tyrosine kinases (RTKs), such as ErbB3, a
member of the epidermal growth factor receptor (EGFR), and insulin-like growth factor-1
receptor. Both of these RTK pathways are frequently deregulated in meningiomas due
to NF2/Merlin loss. Previously, we have shown that NF2-deficient vestibular
schwannomas consistently exhibit higher levels of phosphorylated and activated
ErbB3. In addition, others have reported expression of IGF-1R in the majority of
meningiomas, suggesting that therapies targeting ErbB receptors, IGF-1R, or their
combinations may be novel means of inhibiting the growth of these tumors. Consistent
with this suggestion, we showed that NF2-deficient meningioma cells express ErbB3
and IGF-1R, and that the ErbB3 receptor is constitutively activated in these cells. The
antibodies that targets ErbB3 or both ErbB3 and IGF-1R effectively block IGF-1R and
ErbB3 signaling and inhibit proliferation of meningioma cells in culture. These results
suggest that simultaneous blockade of these RTKs may be a promising new treatment
strategy for meningiomas.
Second, as protein synthesis is a tightly-controlled process that is frequently
deregulated in many tumor types, we investigated natural compounds that are capable
of interfering with the protein translational apparatus. We found that meningiomas
frequently over-expressed all three components of the eukaryotic translation initiation
factor 4F (eIF4F) complex, eIF4A, eIF4E, and eIF4G. Interestingly, from screening a
panel of plant-derived natural compounds for their growth-inhibitory activity in NF2-
deficient meningioma cells, we identified silvestrol, a rocaglamide derivative that blocks
eIF4A activity, as a promising lead agent with an nanomolar IC50 (50% inhibitory
concentration) value. Silvestrol induced G2/M arrest in meningioma cells. Consistently,
silvestrol decreased the levels of multiple cell cycle-associated proteins and mitogenic
kinases. Our results suggest that silvestrol should be further evaluated as another
viable candidate for treating these tumors.
Currently, there is no FDA-approved targeted therapy available for meningiomas. The
availability of a medical therapy that effectively eradicates both NF2-associated and
sporadic meningiomas would significantly advance our efforts to improve clinical care
and long-term treatment outcomes for these patients.”
Long-Sheng Chang, Ph.D.
Center for Childhood Cancer and Blood Diseases, The Research
Institute at Nationwide Children’s Hospital and Department of Pediatrics, The Ohio State University College of Medicine
“Our team will always be grateful for the support shown to us by the Meningioma Mommas. The Mommas provided not only financial assistance to our group but also cheered us on with never-ending enthusiasm. The funds donated to our group allowed us to get a number of pilot projects up and running. These projects helped to produce the necessary preliminary data for several large grants from the National Institutes of Health. This research (which included many Mommas members as study participants) allowed us to report on associations between variables such as hormone replacement therapy, body mass index, family history, dental x-rays, and smoking with meningioma risk. We are also now examining genetic factors associated with risk, including those in meningioma patients treated with therapeutic radiation early in life. With the rapid rise in America’s use of the internet as well as the reduction in funds available for medical research, the need to partner with energetic well-organized patient support groups like the Mommas is imperative and we look forward to working together with the Mommas for years to come.”
Elizabeth Claus, M.D., Ph.D.
Brigham and Women’s Hospital & Instructor, Harvard Medical School
“Without Meningioma Mommas we would not have been able to publish more than 10 articles many key to the world Meningioma literature.”
Michael McDermott, M.D.
Co-director of the Gamma Knife Radiosurgery Program at UCSF Medical Center & Associate Professor of Neurological Surgery at the University of California, San Francisco
“The opportunities provided by the generous grant from Meningioma Mommas have allowed us to look more in depth at a difficult issue in the care of meningioma patients. This pilot study is analyzing the protein expression variances between the different meningioma grade tumors (WHO grades I, II and III). This will be compared to the genomic analysis of these samples. With this data, we can potentially secure further government funding to analyze this on a larger scale. Without the dedication and support of Meningioma Mommas, we would not be able to perform this unique analysis. We look forward to realizing this study and supporting the cause to improve the care of our meningioma patients.”
Garni Barkhoudarian, M.D.
Assistant Professor of Neuroscience / Neurosurgery
Brain Tumor Center & Pituitary Disorders Program
Director: Skull-Base and Endoscopic Microdissection Laboratory
John Wayne Cancer Institute at Saint John’s Health Center
“I am excited to report that the grant money from Meningioma Mommas has proven extremely valuable in our study thus far. We already published our preliminary work using MRI scans to predict the type of meningioma, and we are busily recruiting patients for the next phase of the study which is the prospective analysis. We currently have 11 patients in the study. All of these patients have had the advanced MRI scan, surgery, and pathologic analysis. We plan to present preliminary data at the North American Skull Base Society meeting in Tampa, Florida, in February. We are hoping to recruit more patients to the study and hope to have a total of 20 before publication. In the mean time, I have initiated another study which aims to improve the extent of resection using the concept of fluorescent guided tumor resection. Our preliminary work looks incredible!”
John Lee, M.D. University of Pennsylvania, Philadelphia, PA
Attending Neurosurgeon, Pennsylvania Hospital, University of Pennsylvania, PA
Medical Director, Penn Gamma Knife at Pennsylvania Hospital
Attending Neurosurgeon, Children’s Hospital of Philadelphia, Philadelphia,PA
“The Meningioma Mommas organization has provided my laboratory funding for cutting edge research that would otherwise not be possible through governmental funding agencies that are not willing to take on projects that are early in their development. Their confidence in my work inspires me to work harder to understand the fundamental biology of meningiomas with hope to make better treatments for patients with these tumors.”
Randy Jensen, M.D., Ph.D.
Huntsman Cancer Institute
Departments of Neurosurgery, Radiation Oncology, Oncological Services
University of Utah
“I worked on meningioma research from 2004-2013 during my scientific/academic training in two laboratories, first at UCSF and later at The Johns Hopkins University (JHU). In both labs our research was supported by donations from the Meningioma Mommas Foundation. Their support was essential for the continued investigational work on meningioma research and contributed to important discoveries in the field. The research was mainly devoted to dissecting the cellular and molecular mechanisms driving oncogenesis in these tumors and also developing meningioma models for various purposes, including preclinical testing of potential novel therapeutic drugs.”
“During my work at JHU I was awarded a research grant by the U.S. Department of Defense to explore combinatorial therapeutic opportunities for NF2-mutant meningiomas, building on the meningioma mouse model I previously helped to develop at UCSF. In addition, as a research investigator at JHU, in collaboration with scientists from the Ludwig Cancer Research Institute, I worked on a relevant research project that characterized the expression NY-ESO-1 cancer/testis antigen in meningiomas. The NY-ESO-1 gene is only expressed by germ cells and normally silenced in somatic cells, but it is frequently re-activated in various cancer types. We comprehensively described the expression of NY-ESO-1 in meningiomas and discovered that its expression significantly correlated with malignant tumors and clinical outcome. This relevant discovery was critical for the inclusion of meningioma patients in an ongoing NCI clinical trial testing adoptive T-cell therapy based on the expression of NY-ESO-1. For the last one and half years I have worked at Champions Oncology, Inc, a biotech devoted to personalized oncology solutions for patients.
At Champions I apply my research experience to develop mouse models for translational and personalized therapeutic testing. My training in meningioma research, supported by the Meningioma Mommas Foundation provided me with an excellent opportunity for the development of my scientific career and made it possible to devote my research efforts to translational oncology research. I am just so grateful that the Meningioma Mommas supported my research efforts and positively impacted my career development.”
Gilson Baia, Ph.D., Champions Oncology, Inc.
“I am writing to update the group regarding the results of the survey that was conducted through the meningiomamommas website by members of the group. As the group knows, meningiomas are rather common though we don’t have a complete understanding of them at this moment. In particular, researchers have looked very hard at populations to try and determine the role that hormones may play in the development of meningiomas with mixed results. My wife was diagnosed with a meningioma shortly after the birth of our second daughter which inspired this research. More to the point, the decision whether or not to have more children in the future and how that might change the risk of the meningioma coming back wasn’t known. Unfortunately, a true answer to this question is complicated, but I was struck about how little literature existed to guide the decision.
While struggling with this, I had the good fortune of meeting Dr. Benjamin Craig and his lab, including Michelle Owens. Their expertise allowed for a method to at least start to tackle the situation by finding out what others had been told in a similar situation. We wondered if others desired more children and what doctors may have told them about this. As a physician myself, I am often faced with patients’ requests for advice in the context of insufficient or mixed evidence to guide my recommendation.
As many of you may recall, we developed a survey consisting of the questions we were interested in which would allow some comparison to the general population. We could not have launched this project without the support of Meningioma Mommas, even needing a letter of support in the early days to prove that this research could be completed. We would not have been able to conceive of this without your group being organized and willing to participate. We posted a link to a research survey about 2 years ago.
We are happy to report that the project has resulted in 2 publications. One of these is available online now and the other is in the process of publication. “Birth desires and intentions of those diagnosed with a meningioma” demonstrated that the desire for more children was greater among women with meningioma than those in the general population, but the actual number of these women who go on to have children is lower suggesting that something is leading to this result (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524337/). Our Subsequent manuscript “Women’s Risk of Meningioma Recurrence: the Experiences of a Survivor Support Group” has also been accepted and describes a limited set of outcomes for patients who went on to have children. Due to the small numbers a solid conclusion about risks with subsequent pregnancy cannot be made.
On behalf of the team here at Moffitt, thank you for allowing the survey to be conducted through Meningioma Mommas. Thank you for your time and passion. Keep working towards improving the lives of others living with or yet to be diagnosed with a meningioma. We know there is still much work to be done and we hope our research will inspire others to enter the field or to take it to the next level.”
Damon Reed, MD, Associate Member Moffitt Cancer Canter & Director of the Adolescent and Young Adult Program