Drug target therapy and emerging clinical relevance of exosomes in meningeal tumors

Abstract

Meningioma is the most common central nervous system (CNS) tumor. In recent decades, several efforts have been made to eradicate this disease. Surgery and radiotherapy remain the standard treatment options for these tumors. Drug therapy comes to play its role when both surgery and radiotherapy fail to treat the tumor. This mostly happens when the tumors are close to vital brain structures and are nonbenign. Although a wide variety of chemotherapeutic drugs and molecular targeted drugs such as tyrosine kinase inhibitors, alkylating agents, endocrine drugs, interferon, and targeted molecular pathway inhibitors have been studied, the roles of numerous drugs remain unexplored. Recent interest is growing toward studying and engineering exosomes for the treatment of different types of cancer including meningioma. The latest studies have shown the involvement of exosomes in the theragnostic of various cancers such as the lung and pancreas in the form of biomarkers, drug delivery vehicles, and vaccines. Proper attention to this new emerging technology can be a boon in finding the consistent treatment of meningioma.

Related mechanisms, current treatments, and new perspectives in meningioma

“…The Hedgehog (HH) signaling pathway is an important pathway in embryonic development in vertebrates and also has functions such as regulation of homeostasis and tissue regeneration in adults 112 . This signaling pathway is crucial for tissue growth and repair; incorrect functioning causes uncontrolled cell proliferation 113 . There are three mammalian HH proteins that work on this pathway, known as desert (DHH), Indian (IHH), and sonic (SHH) hedgehog proteins 112 .…”

“…There are three mammalian HH proteins that work on this pathway, known as desert (DHH), Indian (IHH), and sonic (SHH) hedgehog proteins 112 . Of these three proteins, SHH is the most expressed in mammals, and receptor complexes consisting of smoothened (SMO) and patched (PTCH1) proteins are present in this signaling pathway 112,113 . When the HH ligand binds to PTCH1, it suppresses SMO; therefore, the suppressed SMO then interacts with fused homologous suppressor protein (SUFU), activating the glioma‐associated oncogene homolog (GL1) protein to activate target genes 112,113 .…”

“…Of these three proteins, SHH is the most expressed in mammals, and receptor complexes consisting of smoothened (SMO) and patched (PTCH1) proteins are present in this signaling pathway 112,113 . When the HH ligand binds to PTCH1, it suppresses SMO; therefore, the suppressed SMO then interacts with fused homologous suppressor protein (SUFU), activating the glioma‐associated oncogene homolog (GL1) protein to activate target genes 112,113 . SMO mutations are seen in around 5.5% of grade 1 meningiomas without changes in NF2, TRAF7, KLF4, and AKT1 mutations 33,56 .…”

“…SMO is important for cellular activities such as proliferation and angiogenesis, as well as embryogenesis; besides, SMO gain‐of‐function mutations are associated with cancer 56 . Vismodegib and sonidegib are HH inhibitors that work by inhibiting the action of HH ligand cell surface receptors 113 . Vismodegib is studied in a phase II clinical trial under the number NCT02523014 with other drugs, including FAK inhibitor GSK2256098, Akt inhibitor capivasertib, and cyclin‐dependent kinase inhibitor abemaciclib for progressive meningioma 83 …”

“…The Rb signaling pathway regulates DNA replication and cell division in the G1‐to‐S‐phase cell cycle transition 113 . CDK4 and CDK6 kinases interact with cyclin D, regulating the phosphorylation of Rb proteins 121 .…”