Wnt signaling in the tumor microenvironment: A driver of brain tumor dynamics

The Wnt signaling pathway is important for cell growth and development in the central nervous system and its associated vasculature. Thus, it is an interesting factor for establishing anti-brain cancer therapy. However, simply inhibiting the Wnt signaling pathway in patients with brain tumors is not an effective anti-cancer therapy. Due to their complex microenvironment, which comprises various cell types and signaling molecules, brain tumors pose significant challenges. It is important to understand the interplay between tumor cells and the microenvironment for developing effective therapeutic strategies for both benign and malignant brain tumors. Thus, this research focused on the role of the tumor microenvironment (TME) in brain tumor progression, particularly the involvement of Wnt-dependent signaling pathways. The brain parenchyma comprises neurons, glia, endothelial cells, and other extracellular matrix elements that can contribute to the TME. The TME components can secrete Wnt ligands or associated molecules, resulting in the aberrant activation of the Wnt signaling pathway, followed by tumor progression and therapeutic resistance. Therefore, it is essential to understand the intricate crosstalk between the Wnt signaling pathway and the TME in developing targeted therapies. This review aimed to elucidate the complexities of the brain TME and its interactions with the Wnt signaling pathways to improve treatment outcomes and our understanding of brain tumor biology.