Current Perspectives on the Unique Roles of Exosomes in Drug Resistance of Hepatocellular Carcinoma

Dongdong Xue,1 Jingzhao Han,1 Ze Liang,1 Lin Jia,1 Yifan Liu,1,2 Hongfang Tuo,1 Yanhui Peng1 1Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Department of Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yanhui Peng, Department of Hepatobiliary Surgery, Hebei General Hospital, No. 348 Heping West Road, Xinhua District, Shijiazhuang, 050051, Hebei Province, People’s Republic of China, Tel/Fax +86-311-859 8321, Email yhpeng@hebmu.edu.cnAbstract: As a common malignant tumor worldwide, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory, even though treatment methods have improved. Despite the developments in traditional chemotherapy and emerging targeted immunotherapy, the problem of recurrence and metastasis of HCC and adverse effects on survival and prognosis are still serious. Drug resistance is a daunting challenge that impedes HCC treatment. Exosomes, a class of extracellular vesicles ranging in size from 30 to 100 nm, have been the focus of recent studies. Exosomes can activate various signaling pathways and regulate the tumor microenvironment with their cargo, which includes functional lipids, proteins, and nucleic acids. Thus, they change the phenotype of recipient cells via exosome-mediated communication. Exosomes secreted by tumors or stromal cells can also transfer drug-resistant traits to other tumor cells. However, their effects on drug resistance in HCC are not completely understood. In this review, we summarize and discuss the underlying relationship between exosomes and drug resistance in HCC. In addition, we also show that exosomes may act as candidate biomarkers for predicting and monitoring drug responses and as potential targets or vectors to reverse the drug resistance of HCC.Keywords: hepatocellular carcinoma, exosome, tumor microenvironment, targeted therapy