Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer

Abstract

Hepatocellular carcinoma (HCC, also called primary liver cancer) is one of the most fatal cancers in the world. Due to the insidiousness of the onset of HCC and the lack of effective treatment methods, the prognosis of HCC is extremely poor, and the 5-year average survival rate is less than 10%. Exosomes are nano-sized microvesicle and contain various components such as nucleic acids, proteins, and lipids. Exosomes are important carriers for signal transmission or transportation of material from cell to cell or between cells and tissues. In recent years, exosomes have been considered as potential therapeutic targets of HCC. A large number of reports indicate that exosomes play a key role in the establishment of an HCC microenvironment, as well as the development, progression, invasion, metastasis, and even the diagnosis, treatment, and prognosis of HCC. However, the exact molecular mechanisms and roles of exosomes in these processes remain unclear. We believe that elucidation of the regulatory mechanism of HCC-related exosomes and its signaling pathway and analysis of its clinical applications in the diagnosis and treatment of HCC can provide useful clues for future treatment regimens for HCC. This article discusses and summarizes the research progress of HCC-related exosomes and their potential clinical applications.

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

“…Many of the molecular experiments designed to probe the nature of drug resistance in liver cancers showed a crucial role of EVs in this phenomenon [ 188 , 189 ]. There are several mechanisms that modify resistance to pharmacological treatment of liver cancers.…”

Pathogenesis of Viral Hepatitis-Induced Chronic Liver Disease: Role of Extracellular Vesicles

“…Furthermore, they are able to carry a wide range of biological molecules across biological barriers such as the blood-brain barrier, increasing the bioavailability of the molecules in the biological system and reducing the dosage required for therapeutic benefit (Akuma et al, 2019). The structural composition of EVs also provides a protected enclosed space, making it an ideal delivery carrier for gene therapy, anti-fibrotic and cancer treatments (Wang et al, 2019). However, it is worth mentioning that the use of EVs as a drug delivery system is not without limitations.…”

“…There are currently six approved drugs available for treatment of HCC with only moderate success (Jindal et al, 2019). Due to the heterogeneity of the patient population and increasing number of advanced HCC patients showing drug resistance (Niu et al, 2017;Namee and O'Driscoll, 2018;Wang et al, 2019), there is an urgent need to develop innovative therapy for HCC (Jindal et al, 2019). Takahashi et al found a role of EV-associated long non-coding RNAs, linc-ROR, in HCC cells which mediate chemoresistance through attenuation of drug-induced apoptosis and inhibition of p53 expression (Takahashi et al, 2014).…”

“…There are currently six approved drugs available for treatment of HCC with only moderate success ( Jindal et al., 2019 ). Due to the heterogeneity of the patient population and increasing number of advanced HCC patients showing drug resistance ( Niu et al., 2017 ; Namee and O’Driscoll, 2018 ; Wang et al., 2019 ), there is an urgent need to develop innovative therapy for HCC ( Jindal et al., 2019 ). Takahashi et al .…”

Fat mass and obesity-associated protein promotes the tumorigenesis and development of liver cancer

“…Liver cancer is frequently diagnosed at an advanced stage and is often characterized by poor prognosis (3). Consequently, only a small proportion of patients are eligible for potentially curative therapies (4). Various therapeutic strategies are currently used in the management of liver cancer, including surgery, liver transplantation, chemotherapy, radiotherapy and immunotherapy (5)(6)(7)(8)(9)(10)(11)(12).…”