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Review Open Access

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

  • Authors:
    • Mengyan Wei
    • Zelong Cao
    • Liang Dong
    • Wei Wang
    • Mei Wei
    • Lishuang Ji
    • Linan Duan
    • Hui Sun
    • Mingqi Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China, Hebei Key Laboratory of Heart and Metabolism, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China, Department of Orthopedics, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China
    Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 526
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    Published online on: September 16, 2025
       https://doi.org/10.3892/ol.2025.15272
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Abstract

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.
View Figures

Figure 1

Mechanisms of sorafenib resistance in
HCC and RCC. HCC, hepatocellular carcinoma; RCC, renal cell
carcinoma; SLC7A11, solute carrier family 7 member 11; GPX4,
glutathione peroxidase 4; NRF2, NFE2 like BZIP transcription factor
2; TAMs, tumor-associated macrophages; EMT, epithelial-mesenchymal
transition; HIF-1α; hypoxia-inducible factor 1α; xCT,
cystine/glutamate antiporter light-chain subunit.
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Copy and paste a formatted citation
Spandidos Publications style
Wei M, Cao Z, Dong L, Wang W, Wei M, Ji L, Duan L, Sun H and Zheng M: The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review). Oncol Lett 30: 526, 2025.
APA
Wei, M., Cao, Z., Dong, L., Wang, W., Wei, M., Ji, L. ... Zheng, M. (2025). The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review). Oncology Letters, 30, 526. https://doi.org/10.3892/ol.2025.15272
MLA
Wei, M., Cao, Z., Dong, L., Wang, W., Wei, M., Ji, L., Duan, L., Sun, H., Zheng, M."The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review)". Oncology Letters 30.5 (2025): 526.
Chicago
Wei, M., Cao, Z., Dong, L., Wang, W., Wei, M., Ji, L., Duan, L., Sun, H., Zheng, M."The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review)". Oncology Letters 30, no. 5 (2025): 526. https://doi.org/10.3892/ol.2025.15272
Copy and paste a formatted citation
x
Spandidos Publications style
Wei M, Cao Z, Dong L, Wang W, Wei M, Ji L, Duan L, Sun H and Zheng M: The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review). Oncol Lett 30: 526, 2025.
APA
Wei, M., Cao, Z., Dong, L., Wang, W., Wei, M., Ji, L. ... Zheng, M. (2025). The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review). Oncology Letters, 30, 526. https://doi.org/10.3892/ol.2025.15272
MLA
Wei, M., Cao, Z., Dong, L., Wang, W., Wei, M., Ji, L., Duan, L., Sun, H., Zheng, M."The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review)". Oncology Letters 30.5 (2025): 526.
Chicago
Wei, M., Cao, Z., Dong, L., Wang, W., Wei, M., Ji, L., Duan, L., Sun, H., Zheng, M."The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review)". Oncology Letters 30, no. 5 (2025): 526. https://doi.org/10.3892/ol.2025.15272
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