Therapeutic Application of Brain-Specific Angiogenesis Inhibitor 1 for Cancer Therapy

SIMPLE SUMMARY: Brain-specific angiogenesis inhibitor 1 (BAI1) is a transmembrane adhesion GPCR protein that plays an important role in many cellular processes and functions. The ability of BAI1 to promote anti-tumor and anti-angiogenic effects has been explored and developed as a treatment option for several different malignancies. Here, we have detailed a systemic overview of BAI, with a focus on its therapeutic potential for cancer. Due to the recent developments in oncolytic viruses and gene therapeutics towards targeting various types of cancers, our review article is highly relevant to clinical translation. ABSTRACT: Brain-specific angiogenesis inhibitor 1 (BAI1/ADGRB1) is an adhesion G protein-coupled receptor that has been found to play key roles in phagocytosis, inflammation, synaptogenesis, the inhibition of angiogenesis, and myoblast fusion. As the name suggests, it is primarily expressed in the brain, with a high expression in the normal adult and developing brain. Additionally, its expression is reduced in brain cancers, such as glioblastoma (GBM) and peripheral cancers, suggesting that BAI1 is a tumor suppressor gene. Several investigators have demonstrated that the restoration of BAI1 expression in cancer cells results in reduced tumor growth and angiogenesis. Its expression has also been shown to be inversely correlated with tumor progression, neovascularization, and peri-tumoral brain edema. One method of restoring BAI1 expression is by using oncolytic virus (OV) therapy, a strategy which has been tested in various tumor models. Oncolytic herpes simplex viruses engineered to express the secreted fragment of BAI1, called Vasculostatin (Vstat120), have shown potent anti-tumor and anti-angiogenic effects in multiple tumor models. Combining Vstat120-expressing oHSVs with other chemotherapeutic agents has also shown to increase the overall anti-tumor efficacy in both in vitro and in vivo models. In the current review, we describe the structure and function of BAI1 and summarize its application in the context of cancer treatment.