Long Noncoding RNAs as Drivers of Acquired Chemoresistance in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. While recent improvements in the clinical management of HCC have yielded more favorable outcomes for patients, five-year survival rates for these individuals remain poor. Effective treatment of HCC is complicated by a complex disease etiology, significant intertumoral and intratumoral heterogeneity, the frequent absence of early-stage symptoms, and a high potential for metastasis. HCC is highly refractory to chemotherapy, largely due to the acquisition of multidrug resistance, which limits effective pharmacological treatments for HCC patients. While the mechanisms underlying the development of chemoresistance in HCC are diverse, a number of recent studies have positioned long noncoding RNAs (lncRNAs) as key participants in the process. Here, we provide an overview of HCC and the obstacles posed by acquired chemoresistance and summarize the empirical evidence supporting a role for lncRNAs in the development of acquired resistance, focusing on the specific molecular mechanisms by which these molecules attenuate chemosensitivity. We also discuss the contribution of extracellular vesicles as mediators of lncRNA-induced chemoresistance. Although newly emerging, the literature has already yielded important insights into the complex mechanisms by which lncRNAs modulate chemoresistance in HCC.