Roles of anoikis in hepatocellular carcinoma: mechanisms and therapeutic potential

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is a highly aggressive malignancy with limited viable therapeutic options. For early HCC, resection surgery is currently the most effective treatment. However, in advanced stages, resection alone does not sufficiently address the disease, so finding a method with a better prognosis is necessary. Anoikis, known as matrix detachment-induced apoptosis or detachment-induced cell death, is crucial for tissue development and homeostasis. Cancer cells develop means to evade anoikis, e.g. anoikis resistance, thereby allowing for cells to survive under anchorage-independent conditions. HCC cells often acquire resistance to anoikis, allowing them to survive after detaching from the extracellular matrix and contributing to tumor spread. This review discusses the mechanisms of anoikis in HCC, exploring the potential of drug-induced anoikis and targeting anoikis resistance as promising therapeutic strategies for treating HCC, analyzing the value of anoikis in the immune of HCC, and propose potential pathways in oncotherapy, which can provide background knowledge for subsequent related research.