Role of N6-methyladenosine in tumor neovascularization

Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m⁶A) modification in regulating these processes. This review explores the mechanisms by which m⁶A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m⁶A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m⁶A in vascular-immune crosstalk. Finally, we discuss the current development of m⁶A inhibitors and their potential applications, along with the contribution of m⁶A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m⁶A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m⁶A modulation in cancer treatment. By understanding the intricate role of m⁶A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m⁶A offers a novel approach to interfere with the tumor's ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression.