Challenges and Opportunities in Future Meningioma Research and Care

CHAPTER 64 Challenges and Opportunities in Future Meningioma Research and Care

Peter M. Black, Rudolf Fahlbusch, M. Necmettin Pamir

INTRODUCTION

There has never been a more exciting time in meningioma research and care. As analytic tools improve and interest grows, great strides can occur toward understanding and treating meningiomas. Patient advocacy and funding agency interest will help to generate better and better paradigms for management and the analytic tools are increasingly available. This chapter discusses some future possibilities in basic and translational research, pathology, imaging, surgical management, radiation, chemotherapy, and outcome analysis.

BASIC AND TRANSLATIONAL RESEARCH

Basic research is the engine that drives the future development of medical care. For meningiomas, it involves not only molecular biology but also epidemiology, new therapeutic agents, non-invasive surgical techniques, side effects of treatment, and a host of other topics. Often the greatest improvements are made when techniques allow a definitive to answer to some long-standing questions. We now have very powerful molecular techniques, and many of them are just awaiting application to meningiomas. Modern molecular biology and genetics can significantly support research on the oncogenesis, epidemiology, diagnosis, treatment, and follow-up of meningiomas. At present, techniques of single-nucleotide polymorphism (SNP) analysis, high-throughput screening for molecular profiling, and proteomics have been applied to other tumors with great success. Only personnel and interest among investigators are needed to apply these techniques in meningioma research. Here are some of the questions that should be answerable in the next 10 years:

Our current understanding on the molecular oncogenesis of meningiomas is still very immature. A clonal origin and a stepwise progression to more malignant forms have been suggested by molecular biological studies in the last few decades. However, the origins of the initiation, persistence, and progression of oncogenesis are still not known. We still do not know the determinants of cardinal steps of cancer in meningioma oncogenesis, the self-sufficiency in growth signals, the insensitivity to antigrowth signals, evasion of apoptosis, sustained angiogenesis, limitless replicative potential, and tissue invasion and metastasis.
Can we identify a molecular “fingerprint” for some meningiomas that makes them aggressive from the beginning even though they seem grade 1?
What is the role of sex hormone receptors in meningioma pathogenesis?
What is the role of genes other than those on chromosome 22 in initiating meningiomas and driving them to progress?
Advances in molecular biology and genetics can lead to a molecular classification of meningiomas? Such a classification using DNA, mRNA, or protein analysis can improve our understanding and treatment.
Are there meningioma “stem cells” that are the primary cell of origin of the tumor? The presence of such tumor initiating cells have been proposed in many cancers including gliomas, and this discovery has led to hypotheses that could explain peculiar clinical behaviors seen in gliomas such as radiation insensitivity, perivascular spread, and angiogenetic potential. The presence of such tumor initiating progenitor cells has not been adequately tested in meningiomas.
Can we develop an in vivo meningioma model that will allow drug and other studies to accurately reflect the human tumor? Such in vitro or in vivo models including transgenic mouse models that carry the genetic alterations commonly seen in meningiomas will both boost the understanding of meningioma oncogenesis and will be a very practical means for optimizing existing classical therapies and exploring new biological treatment modalities.
Meningiomas are very vascular tumors and their growth is very much influenced by their vascular supply? Our current understanding of the angiogenetic potential of meningiomas and the role of antiangiogenic therapies remains limited. In addition, the role of angiogenesis in the mechanism of action of existing therapies such as radiosurgery remains to be better defined to improve and refine such treatments. Angiogenesis research remains a very important focus of interest in meningioma research.
Are there particular receptor abnormalities in atypical meningiomas that can be used as targets for biological therapies?
The result of this kind of analysis may be the development of personalized meningioma care? Enough will be known about the patient’s genes, the tumor’s molecular characteristics, and the treatments available that we can individualize treatment and prediction of outcome for a specific patient.

EPIDEMIOLOGY

One of the most important areas for meningioma research is epidemiology, including molecular epidemiology. Despite almost a century of ongoing research, there are still numerous unknowns regarding the epidemiology of meningiomas. A striking example is that we still do not know which meningiomas will grow after diagnosis and which will not, and the clinician regularly faces several of these dilemmas in daily practice. Classical epidemiology studies such as the INTERPHONE study and other large-scale studies of causal or permissive factors in meningiomas are important contributions to the literature. The INTERPHONE study is the largest case control study to date to examine the risks of mobile-phone use and includes more than 2400 meningioma cases. Also in 2005, the NIH funded a very large study led by Dr. Elizabeth Claus, which will begin to answer several ongoing questions in meningioma pathogenesis:

What effects do pregnancy, oral contraceptives, and hormone replacement therapy have on meningioma formation?
Is cell phone use related to meningioma development?

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Aug 5, 2016 | Posted by in NEUROSURGERY | Comments Off on Challenges and Opportunities in Future Meningioma Research and Care

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