Background: Most of the drugs are metabolized in the liver by the action of drug metabolizing enzymes.
In hepatocellular carcinoma (HCC), primary drug metabolizing enzymes are severely dysregulated, leading to failure
of chemotherapy. Sorafenib is the only standard systemic drug available, but it still presents certain limitations, and
much effort is required to understand who is responsive and who is refractory to the drug. Preventive and therapeutic
approaches other than systemic chemotherapy include vaccination, chemoprevention, liver transplantation, surgical
resection, and locoregional therapies.
Objectives: This review details the dysregulation of primary drug metabolizing enzymes and drug transport proteins
of the liver in HCC and their influence on chemotherapeutic drugs. Furthermore, it emphasizes the adoption of safe
alternative therapeutic strategies to chemotherapy.
Conclusion: The future of HCC treatment should emphasize on understanding of resistance mechanisms and the
finding of novel, safe, and efficacious therapeutic strategies, which will surely benefit patients affected by advanced