Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma

Abstract

Glioblastoma (GBM) is a devastating type of brain tumor, and current therapeutic treatments, including surgery, chemotherapy, and radiation, are palliative at best. The design of effective and targeted chemotherapeutic strategies for the treatment of GBM require a thorough analysis of specific signaling pathways to identify those serving as drivers of GBM progression and invasion. The Wnt/β-catenin and PI3K/Akt/mTOR (PAM) signaling pathways are key regulators of important biological functions that include cell proliferation, epithelial–mesenchymal transition (EMT), metabolism, and angiogenesis. Targeting specific regulatory components of the Wnt/β-catenin and PAM pathways has the potential to disrupt critical brain tumor cell functions to achieve critical advancements in alternative GBM treatment strategies to enhance the survival rate of GBM patients. In this review, we emphasize the importance of the Wnt/β-catenin and PAM pathways for GBM invasion into brain tissue and explore their potential as therapeutic targets.

Lichen Secondary Metabolites Inhibit the Wnt/β-Catenin Pathway in Glioblastoma Cells and Improve the Anticancer Effects of Temozolomide

“…Another important factor contributing to the GBM chemo- and radiotherapy resistance is the hyperactivated Wnt/β-catenin pathway [ 11 , 28 ]. Thus, this signaling pathway has become the novel drug target for GBM treatment [ 11 , 12 , 29 ].…”

Dynamic Involvement of Telocytes in Modulating Multiple Signaling Pathways in Cardiac Cytoarchitecture

“…The emblem of the non-canonical signaling pathway is its beta-catenin-autonomous exertions [ 50 ]. The DVL-c-Jun N terminal kinase (JNK) pathway/PCP pathway is required in cellular polarity [ 51 ]. Of the members of the WNT family of glycoproteins, WNT5a is one of the most eminently scrutinized non-canonical members.…”

“…Of the members of the WNT family of glycoproteins, WNT5a is one of the most eminently scrutinized non-canonical members. Once WNT interacts with FZD along DVL to assemble a complex with the Disheveled-associated activator of morphogenesis (DAAM), the JNK kinase pathway is activated, proceeding with cytoskeletal rearrangements [ 51 ]. In addition, DAAM propels RhoA, which further actuates Rho-associated protein kinase (ROCK) [ 51 , 52 ].…”

“…Once WNT interacts with FZD along DVL to assemble a complex with the Disheveled-associated activator of morphogenesis (DAAM), the JNK kinase pathway is activated, proceeding with cytoskeletal rearrangements [ 51 ]. In addition, DAAM propels RhoA, which further actuates Rho-associated protein kinase (ROCK) [ 51 , 52 ]. In the non-canonical WNT/Ca 2+ signaling, the cooperation between the ROR/RYK co-receptor and WNT/FZD generates the setout of Diacylglycerol (DAG) and Inositol trisphosphate (IP3) [ 51 , 53 , 54 ].…”

“…In addition, DAAM propels RhoA, which further actuates Rho-associated protein kinase (ROCK) [ 51 , 52 ]. In the non-canonical WNT/Ca 2+ signaling, the cooperation between the ROR/RYK co-receptor and WNT/FZD generates the setout of Diacylglycerol (DAG) and Inositol trisphosphate (IP3) [ 51 , 53 , 54 ]. DAG activates Protein kinase C (PKC) [ 54 ].…”