VAV1 targeting for cancer therapeutics: mechanistic understanding and preclinical promise

INTRODUCTION: Vav1, although mainly expressed in hematopoietic cells where it participates in the regulation of signaling pathways downstream of numerous cell surface receptors, has been found mutated and ectopically expressed in many human cancers where it drives tumor proliferation. Thus, mechanisms aimed at targeting Vav1 could have therapeutic benefit in cancers where it is aberrantly expressed in either a wild type or mutant form. AREAS COVERED: This review describes and summarizes the expanding cellular and molecular mechanisms by which Vav1 contributes to tumor development, proliferation and survival in human cancers within and outside the hematopoietic lineages. We will discuss the emerging role of Vav1 as an oncogenic driver in many human tumors and the current studies aimed at identifying various therapeutics to target this protein and the pathways it regulates. EXPERT OPINION: Targeting Vav1 comes with several challenges due to its role in regulating signaling in immune cells, so any small molecule or other approaches need to balance targeting this molecule in cancer and sparing effects on the immune system where it might be participating in a positive role in anti-tumor immunity. Furthermore, the role of the other Vav family members in Vav1-expressing or mutated cancer needs to be addressed.