Decoding the functional role of extracellular vesicles in hepatocellular carcinoma: implications in clinical theranostics

Abstract

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in adults, the sixth most commonly diagnosed neoplasia, and the third leading cause of cancer-related deaths worldwide. Despite tangible mechanistic insights gained from clinical profiling data and experimental models, our knowledge on the molecular pathogenesis of HCC remains limited. Recent efforts directed toward reevaluating molecular pathways underlying HCC tumorigenesis and metastasis have been revolutionized by the discovery of extracellular vesicles (EVs) and their diverse pleiotropic roles in local and distant failures. In the past decade, EVs have emerged as versatile and critical intercellular cancer signalosomes that can induce malignant transformation and govern distant metastasis. New studies have begun to unravel the potential of EV-mediated regulatory mechanisms, coopted by tumor cells, in shaping favorable tumor microenvironments and defining the landscape of cancer metastasis-promoting systems. In this chapter, we outline the multifaceted roles of EVs in establishing fertile tumor milieu to promote the development and metastatic organotropism in HCC. Finally, we summarize current advancements in the application of EVs as clinical theranostic agents for subverting the development and progression of HCC.