A Monoclonal Antibody Against β1 Integrin Inhibits Proliferation and Increases Survival in an Orthotopic Model of High-Grade Meningioma

Nigim, Fares; Kiyokawa, Juri; Gurtner, Alessandra; Kawamura, Yoichiro; Hua, Lingyang; Kasper, Ekkehard M.; Brastianos, Priscilla K.; Cahill, Daniel P.; Rabkin, Samuel D.; Martuza, Robert L.; Carbonell, W. Shawn; Wakimoto, Hiroaki

doi:10.1007/s11523-019-00654-4

Cited by 12 publications

(8 citation statements)

References 43 publications

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“…As in other cancers, the PI3K/ AKT pathway has been implicated in meningiomas, with involvement in cell-cell and cell-ECM interaction through integrin signaling [65,99], in the regulation of cytoskeletal integrity [38] and the interplay of proteases and their inhibitors, specifically MMP-9 [88]. Similarly, the focal adhesion kinase (FAK) and its broad downstream effects have been shown to influence migration and invasion after activation through integrins, growth factors, and other ECM components [50,51,71,88,100,101]. Other pathways involved include the mitogen-activated protein kinase (MAPK) [88,99] and the Hippo pathways [102].…”

Section: T R a Nsc R I P T Ion Fac Tor S A N D Signa Li Ngmentioning

confidence: 99%

Molecular neuropathology of brain‐invasive meningiomas

et al. 2022

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Invasion of brain tissue by meningiomas has been identified as one key factor for meningioma recurrence. The identification of meningioma tumor tissue surrounded by brain tissue in neurosurgical samples has been touted as a criterion for atypical meningioma (CNS WHO grade 2), but is only rarely seen in the absence of other high‐grade features, with brain‐invasive otherwise benign (BIOB) meningiomas remaining controversial. While post‐surgery irradiation therapy might be initiated in brain‐invasive meningiomas to prevent recurrences, specific treatment approaches targeting key molecules involved in the invasive process are not established. Here we have compiled the current knowledge about mechanisms supporting brain tissue invasion by meningiomas and summarize preclinical models studying targeted therapies with potential inhibitory effects.

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Section: T R a Nsc R I P T Ion Fac Tor S A N D Signa Li Ngmentioning

confidence: 99%

Molecular neuropathology of brain‐invasive meningiomas

et al. 2022

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“…In addition, those monoclonal multiple meningiomas can acquire inter-tumor heterogeneity due to additional somatic alterations through branched evolution (35). Nigim et al analyzed the expression of b1 integrin of clinical meningioma specimens and found in vivo murine model utilizing two patient-derived high grade meningioma xenografts, that antibody therapy targeting b1 integrin decreased high grade meningioma cells proliferation and extended overall survival (36). A preclinical study found that 9% of 108 meningiomas demonstrated mutations in the PI3K/ AKT/mTOR pathway, suggesting it may play an important role in the growth of meningiomas (37).…”

Section: Molecular Features In Meningiomasmentioning

confidence: 99%

Molecular determinants of outcomes in meningiomas

et al. 2022

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Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.

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“…The activity of the molecule is controlled by a series of pathways that integrate various growth factors [23]. Furthermore, contact inhibition is an additional mechanism that enacts molecular modulation of NF2 to prevent or promote cell growth [24][25][26][27][28]. A wide variety of downstream pathways are involved in the control of proliferation, and its relation to mTORC1 [19,21].…”

Section: The Nf2 Pathwaymentioning

confidence: 99%

“…Contact inhibition, an important mechanism in meningeal cells, is reported to be involved in the upstream regulation of the protein. The contact inhibition is mediated by multiple proteins, such as RTKs, CD44, and integrin beta-1 [24][25][26][27][28]. (*) The ensuing activation of the merlin protein leads to mTORC1 inhibition through a poorly understood mechanism [22,23].…”

Section: The Pi3k/akt Pathwaymentioning

confidence: 99%

mTOR Signaling and Potential Therapeutic Targeting in Meningioma

Pinker

Barciszewska

2022

IJMS

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Meningiomas are the most frequent primary tumors arising in the central nervous system. They typically follow a benign course, with an excellent prognosis for grade I lesions through surgical intervention. Although radiotherapy is a good option for recurrent, progressive, or inoperable tumors, alternative treatments are very limited. mTOR is a protein complex with increasing therapeutical potential as a target in cancer. The current understanding of the mTOR pathway heavily involves it in the development of meningioma. Its activation is strongly dependent on PI3K/Akt signaling and the merlin protein. Both factors are commonly defective in meningioma cells, which indicates their likely function in tumor growth. Furthermore, regarding molecular tumorigenesis, the kinase activity of the mTORC1 complex inhibits many components of the autophagosome, such as the ULK1 or Beclin complexes. mTOR contributes to redox homeostasis, a vital component of neoplasia. Recent clinical trials have investigated novel chemotherapeutic agents for mTOR inhibition, showing promising results in resistant or recurrent meningiomas.

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A Monoclonal Antibody Against β1 Integrin Inhibits Proliferation and Increases Survival in an Orthotopic Model of High-Grade Meningioma

Cited by 12 publications

References 43 publications

Molecular neuropathology of brain‐invasive meningiomas

Molecular neuropathology of brain‐invasive meningiomas

Molecular determinants of outcomes in meningiomas

mTOR Signaling and Potential Therapeutic Targeting in Meningioma

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