An emerging role of radiation‑induced exosomes in hepatocellular carcinoma progression and radioresistance (Review)

Abstract

The incidence rates of hepatocellular carcinoma (HCC) worldwide are increasing, and the role of radiotherapy is currently under discussion. Radioresistance is one of the most important challenges in the therapy of HCC compared with other local advanced, recurrent and metastatic cancers. The mechanisms of radioresistance are complex and remain to be fully understood; however, extracellular vesicles have been investigated in recent studies. Exosomes, which are 40-to 150-nm extracellular vesicles released by cancer cells, contain multiple pathogenic components, including proteins, nucleic acids and lipids, and play critical functions in cancer progression. Emerging data indicate a diagnosis potential for exosomes in HCC, since radiation-derived exosomes promote radioresistance. Radiation-based therapy alters the contents and components of exosomes, suggesting that exosomes and their components may serve as prognostic and predictive biomarkers to monitor radiation response. Therefore, understanding the roles and mechanisms of exosomes in HCC progression and radiation response during HCC therapy may increase our knowledge concerning the roles of exosomes in radioresistance, and may lead to novel approaches for HCC prognosis and treatment. The current review summarizes recent studies on exosome involvement in HCC and the molecular changes in exosome components during HCC progression. It also discusses the functions of exosomes in HCC therapy, and highlights the importance of exosomes in HCC progression and resistance for the development of novel therapies.

Boron Neutron Capture Therapy Eliminates Radioresistant Liver Cancer Cells by Targeting DNA Damage and Repair Responses

“… 36 For patients receiving radiotherapy, radioresistance is one of the most important challenges in the management of HCC. 12 In the present study, we demonstrated the feasibility of BNCT to overcome the radioresistance of HCC. BNCT efficiently eliminated HepG2-R cells, which resisted γ-ray irradiation at the same dose.…”

“… 9 , 10 Moreover, the effectiveness of RT can be compromised by radioresistance. 11 , 12 Although immunotherapy has emerged as a breakthrough in HCC treatment, there are still some challenges, such as the low response rate, uncertain efficacy, and side effects. 13 , 14 Consequently, it is necessary to develop an effective therapy for recurrent advanced HCC.…”

Clinical Application of Small Extracellular Vesicles in Gynecologic Malignancy Treatments

“… Principles and applications of sEVs in cancer therapy. ( a ) sEV contents induce chemo [ 14 ], radiation [ 16 ], and targeted therapy resistance [ 17 ] by changing the sensitivity of recipient cells through intercellular communication; ( b ) sEVs can regulate angiogenesis [ 17 , 18 ] and vascular permeability [ 19 , 20 ] by influencing the behavior of endothelial cells that line blood vessels; ( c ) sEVs can regulate the evasion [ 21 ] and infiltration [ 22 ] of immune cells by stimulating or suppressing immune responses, that is, they have the ability to act as immunomodulators [ 23 ]; ( d ) direct incubation of sEVs with cargo [ 24 ] or sEVs with surface engineering [ 25 ] can achieve the function of therapeutic cargo packing and targeted therapy (Created with (accessed on 26 February 2023)). …”

The role of exosomes in therapeutic resistance of hepatocellular carcinoma

“…The mechanisms underlying radioresistance are complex, involving various factors such as radiation-induced DNA damage repair, apoptosis escape, cell cycle arrest, abnormal autophagy, abundance of cancer stem cells, and other dysregulated biological processes [61] . Radioresistance is also highly associated with TME, a critical factor influencing tumor progression and therapeutic response, which can be modulated through intercellular communications mediated by exosomes [62,63] .…”