Glioblastoma (GBM) is an aggressive brain tumor characterized by cellular and molecular diversity. This diversity presents significant challenges for treat

Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression. This review uncovers the complexity of immunomodulatory genes splicing dysregulation in oncogenesis. Identifying specific immunomodulatory splicing isoforms that contribute to cancer could be utilized to improve current immunotherapeutic drugs or develop novel therapeutic interventions for cancer.

Protein arginine methylation is an epigenetic modification involved in transcription, splicing and signal transduction and is mediated by protein arginine methyltransferases (PRMTs). PRMTs regulate various tumor angiogenesis pathways, including vascular endothelial growth factor receptor-2 (VEGFR-2) signaling. PRMT1, PRMT4, and PRMT5 activate distinct stages of angiogenesis. For example, inhibiting PRMT5 suppresses VEGF-induced vessel sprouting in experimental models while impairing hypoxia-inducible factor 1-alpha (HIF-1α) stability and VEGFR-2 phosphorylation. PRMT1 and PRMT4 similarly influence VEGF isoform expression, leading to increased angiogenesis. Targeting PRMTs in experimental models results in suppressed angiogenesis and reduced cancer progression. Several small-molecule PRMT inhibitors, including GSK3326595 and EPZ015666, have entered early-phase clinical trials for solid tumors. These agents show promise in inhibiting tumor angiogenesis, although there are toxicity concerns. This review examines the mechanistic basis and therapeutic rationale for targeting PRMTs in breast cancer and discusses combination approaches to overcome resistance. We integrate preclinical and emerging clinical data to highlight the potential antiangiogenic and tumor-suppressive effects of PRMT inhibitors, providing insights for future therapeutic strategies for breast cancer.