Sorafenib for hepatocellular carcinoma: potential molecular targets and resistance mechanisms

Hepatocellular carcinoma (HCC) is the most widespread typical therapy-resistant, unresectable type of malignant solid tumour with a high death rate constituting huge medical concern. Sorafenib is a small molecule oral multi-target kinase potent inhibitor that acts by suppressing/blocking the multiplication of the tumour cells, angiogenesis, and encouraging apoptosis of the tumour cells. Though, the precise mechanism of tumour cell death induction by sorafenib is yet under exploration. Furthermore, genetic heterogeneity plays a critical role in developing sorafenib resistance, which leads the way to identify the need for predictive biomarkers responsible for drug resistance. Therefore, it is essential to find out the fundamental resistance mechanisms to expand therapeutic plans. The authors summarize the molecular concepts of resistance, progression, potential molecular targets, HCC management therapies, and discussion on the advancements expected in the coming future, inclusive of biomarker-driven treatment strategies, which may provide the prospects to design innovative therapeutically targeted strategies for the HCC treatment and the clinical implementation of emerging targeted agents.

Automated summary

Hepatocellular carcinoma is a challenging type of malignant solid tumors that are therapy-resistant and unresectable, with genetic heterogeneity playing a critical role in developing drug resistance. The authors' summary of molecular concepts and potential targets provides insights into potential biomarkers and innovative targeted strategies for HCC treatment.