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Small-molecule-based targeted therapy in liver cancer
Yue Ming1, Yanqiu Gong2, Xuewen Fu3
1Laboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610064, China.
Abstract:
Liver cancer is one of the most prevalent malignant tumors worldwide. According to the Barcelona Clinic Liver Cancer staging criteria, clinical guidelines provide tutorials to clinical management of liver cancer at their individual stages. However, most patients diagnosed with liver cancer are at advanced stage; therefore, many researchers conduct investigations on targeted therapy, aiming to improve the overall survival of these patients. To date, small-molecule-based targeted therapies are highly recommended (first line: sorafenib and lenvatinib; second line: regorafenib and cabozantinib) by current the clinical guidelines of the American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network. Herein, we summarize the small-molecule-based targeted therapies in liver cancer, including the approved and preclinical therapies as well as the therapies under clinical trials, and introduce their history of discovery, clinical trials, indications, and molecular mechanisms. For drug resistance, the revealed mechanisms of action and the combination therapies are also discussed. In fact, the known small-molecule-based therapies still have limited clinical benefits to liver cancer patients. Therefore, we analyze the current status and give our ideas for the urgent issues and future directions in this field, suggesting clues for novel techniques in liver cancer treatment.
Insights
Small-molecule targeted therapies offer new hope for advanced liver cancer patients. Research explores approved, preclinical, and investigational treatments, aiming to overcome drug resistance and improve survival rates.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Liver cancer is a leading global malignancy, often diagnosed at advanced stages.
- Current clinical guidelines recommend small-molecule targeted therapies like sorafenib and lenvatinib as first-line treatments.
- Despite advancements, existing therapies provide limited clinical benefits for many liver cancer patients.
Purpose of the Study:
- To summarize current and emerging small-molecule targeted therapies for liver cancer.
- To review the discovery, clinical trials, mechanisms, and resistance patterns of these therapies.
- To analyze the current landscape and propose future directions for liver cancer treatment.
Main Methods:
- Literature review of approved, preclinical, and investigational small-molecule targeted therapies.
- Analysis of clinical trial data, molecular mechanisms, and drug resistance.
- Discussion of combination therapies and future research avenues.
Main Results:
- Key small-molecule targeted therapies (sorafenib, lenvatinib, regorafenib, cabozantinib) are established first- and second-line treatments.
- Ongoing research investigates novel agents and combination strategies to enhance efficacy.
- Mechanisms of drug resistance are being elucidated, guiding the development of overcoming strategies.
Conclusions:
- Small-molecule targeted therapies represent a critical approach in liver cancer management.
- Addressing drug resistance and exploring novel therapeutic combinations are essential for improving patient outcomes.
- Further research is needed to identify more effective treatments and novel techniques for liver cancer.
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