CHAPTER 64 Challenges and Opportunities in Future Meningioma Research and Care
BASIC AND TRANSLATIONAL RESEARCH
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 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?
