The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review)

Sorafenib, a multi‑target tyrosine kinase inhibitor, is widely used for the treatment of advanced hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The present review explores the potential of sorafenib combination therapy to overcome drug resistance, mitigate toxicity and enhance efficacy. Sorafenib inhibits tumor growth and angiogenesis but is often limited by rapid resistance development and severe side effects. Combination therapies involving inhibitors of the PI3K/AKT/mTOR pathway, oxidative stress and autophagy inhibitors show promise in improving antitumor efficacy, reducing resistance and lowering toxicity. However, challenges such as complex drug interactions, increased treatment costs and a lack of long‑term clinical data remain. Future research should focus on personalized combination strategies, exploring new molecular targets and performing large‑scale clinical trials to optimize the safety and efficacy of sorafenib combination therapies, ultimately advancing cancer treatment and improving patient outcomes.