Spotlights on extracellular vesicles in hepatocellular carcinoma diagnosis and treatment: an update review

Abstract

Hepatocellular carcinoma (HCC), one of the most prevalent cancers, with a high mortality rate worldwide, seriously impairs patient health. The lack of accurate targets impedes the early screening and diagnosis of HCC and is associated with a poor response to routine therapies. Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are lipid bilayer membrane-derived nanometer-sized vesicles. EVs can be secreted from various cancer cells and release diverse biomolecules, such as DNA, RNA, proteins, metabolites, and lipids, making them a potential source of biomarkers and regulators of the tumor microenvironment. Emerging evidence suggests that EVs are involved in intercellular communication by carrying biological information. These EVs elicit physiological functions and are involved in the oncogenesis of HCC, such as proliferation, invasion, metastasis, and chemoresistance of HCC. EVs have also been considered promising biomarkers and nanotherapeutic targets for HCC. Therefore, this review sheds light on the current understanding of the interactions between EVs and HCC to propose potential biomarkers and nanotherapeutic strategies.

Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics

“…The therapeutic potential of EVs in HCC is a subject of increasing scientific interest and holds promise for innovative diagnostic and therapeutic interventions [32,143,144]. Within the context of HCC, EVs have emerged as key players in the intricate network of intercellular communication within the tumor microenvironment [15,145,146].…”

Extracellular vesicles as tools and targets in therapy for diseases

“…The complete analysis and screening of urinary EVs revealed that the glycoproteins LG3BP, PIGR, and KNG1 were highly elevated in these EVs obtained from the urine of HCC patients, but ASPP2 was dramatically reduced in these EVs. 222 SMAD3, one of the molecules involved in HCC metastasis, also offers diagnostic potential for HCC, discriminating HCC from healthy to benign hepatoma 223 .…”

“…Likewise, it has been demonstrated that miR-638 in EVs is a diagnostic for HCC diagnosis and an independent predictive factor for HCC patients. 222 …”

“…Likewise, it has been demonstrated that miR-638 in EVs is a diagnostic for HCC diagnosis and an independent predictive factor for HCC patients. 222 Immune evasion and establishment of pre-metastatic niche by extracellular vesicles TDEVs have been demonstrated to influence non-cancerous and cancer cells, creating a TME conducive to tumor growth and metastasis. TDEVs impact cancer cells by promoting angiogenesis, which is crucial for tumor formation and metastatic spread, and by increasing vascular permeability, facilitating the dissemination of cancer cells.…”

Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

“…Chemotherapy is an option for patients with advanced HCC, but insensitivity to chemotherapeutic agents leads to poor treatment outcomes. Moreover, resistant cells secrete and deliver exosomes to sensitive cells, facilitating angiogenesis and EMT, further inducing multidrug resistance [134]. Thus, exosome-based treatments for tumor resistance appear feasible and have achieved preliminary efficacy in colorectal cancer [135][136][137], although such treatments have not yet been reported in hepatitis B-related liver cancer.…”