Combating drug resistance in hepatocellular carcinoma: No awareness today, no action tomorrow

Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide, is associated with a high degree of malignancy and poor prognosis. Patients with early HCC may benefit from surgical resection to remove tumor tissue and a margin of healthy tissue surrounding it. Unfortunately, most patients with HCC are diagnosed at an advanced or distant stage, at which point resection is not feasible. Systemic therapy is now routinely prescribed to patients with advanced HCC; however, drug resistance has become a major obstacle to the treatment of HCC and exploring purported mechanisms promoting drug resistance remains a challenge. Here, we focus on the determinants of drug resistance from the perspective of non-coding RNAs (ncRNAs), liver cancer stem cells (LCSCs), autophagy, epithelial-mesenchymal transition (EMT), exosomes, ferroptosis, and the tumor microenvironment (TME), with the aim to provide new insights into HCC treatment.