Meningioma

The meninges are the membranes that surround the brain and spinal cord and a meningioma is a tumor that develops from the meninges. Meningiomas account for approximately 27% of primary brain tumors and are very common tumors of this type. Most meningiomas (90%) are classified as benign tumors, with the remaining 10% being atypical or malignant. In many cases, benign meningiomas grow slowly. This means that depending on the location of the meningioma, it may have reached a relatively large size before it causes symptoms.

Figure 1. Typical mutations by WHO classification and anatomical location. (Al-Rashed, M., et al., 2020)

The mainstay of meningioma treatment is a combination of radiotherapy and surgery, but suffers from low efficacy, short response times to treatment, lack of uniform response criteria, and a limited role for systemic therapy. As with other primary and metastatic brain tumors, the future of immune-based therapeutic approaches to meningiomas remains promising.

• Detection of molecular alterations

With the advent of next-generation sequencing technologies, driver mutations have been identified in the underlying pathogenesis of malignant and recurrent sporadic meningiomas. Alfa Cytology has provided analysis services for molecular alterations in meningiomas, including neurofibromatosis type 2 (NF2) oncogenic mutations, chromosomal abnormalities, additional somatic mutations, AKT and SMO pathways, TRAF7 and KLF4 pathways, and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Although these mutations may only occur in a small number of meningiomas, a better understanding of these pathways may ultimately provide options for improved systemic management throughout the body.

• Therapies using the immune system

Programmed death-1 (PD-1) is expressed on activated T and B cells, while its primary ligand (PD-L1) is expressed on macrophages but can be induced by inflammatory cytokines. Activated T cells expressing PD-1 are involved in PD-L1, leading to diminished T cell effector function. Alfa Cytology can help you characterize the immune microenvironment of mesenchymal meningiomas and support you in using immune checkpoint blockade as a potential therapeutic approach. In addition, there is growing evidence that tumors with a high mutational load are more sensitive to treatment with checkpoint inhibitors. As high-grade meningiomas, particularly after radiation therapy, have more molecular alterations and mutations, they may be particularly sensitive to this treatment.

• Targeted and anti-angiogenic therapy

Dysregulation of the cell cycle has been identified as an important cause of tumor growth and progression across multiple tumor types. As seen in other systemic malignancies, key factors in these pathways such as MAPK and PI3K have been well characterized as having oncogenic effects and therefore could be used as current and potential treatments for these cancers. Alfa Cytology is also actively progressing its research program into the role of meningiomas and the optimistic view is that they are also potential targets.

The development of effective drug treatments for recurrent and treatment-refractory meningiomas has been challenged and limited by a variety of factors. With advances in genomics and the identification of driver mutations, Alfa Cytology has helped researchers in this field to progressively advance their research into targeted drugs. Considering the research on new drugs, identifying and understanding new signaling pathways and factors will hopefully provide ideas for drug development. Please feel free to contact us to advance trials and accelerate the development of new therapies for meningioma patients.

Reference

1. Al-Rashed, M., et al. (2020). "Recent Advances in Meningioma Immunogenetics." Frontiers in Oncology, 9:1472.