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Rethinking therapeutic strategies of dual-target drugs: An update on pharmacological small-molecule compounds in
Yiren Yang1,2, Yi Mou1, Lin-Xi Wan3
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, and Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China.
Abstract:
Oncogenes and tumor suppressors are well-known to orchestrate several signaling cascades, regulate extracellular and intracellular stimuli, and ultimately control the fate of cancer cells. Accumulating evidence has recently revealed that perturbation of these key modulators by mutations or abnormal protein expressions are closely associated with drug resistance in cancer therapy; however, the inherent drug resistance or compensatory mechanism remains to be clarified for targeted drug discovery. Thus, dual-target drug development has been widely reported to be a promising therapeutic strategy for improving drug efficiency or overcoming resistance mechanisms. In this review, we provide an overview of the therapeutic strategies of dual-target drugs, especially focusing on pharmacological small-molecule compounds in cancer, including small molecules targeting mutation resistance, compensatory mechanisms, synthetic lethality, synergistic effects, and other new emerging strategies. Together, these therapeutic strategies of dual-target drugs would shed light on discovering more novel candidate small-molecule drugs for the future cancer treatment.
Insights
Dual-target drug development offers a promising strategy to overcome cancer drug resistance by targeting mutations and compensatory mechanisms. This approach focuses on small-molecule compounds for improved cancer therapy and future drug discovery.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Oncogenes and tumor suppressors regulate cancer cell fate.
- Mutations and abnormal protein expression in these genes are linked to cancer drug resistance.
- Understanding inherent resistance and compensatory mechanisms is crucial for targeted drug discovery.
Purpose of the Study:
- To review therapeutic strategies of dual-target drugs in cancer treatment.
- To focus on pharmacological small-molecule compounds for dual-targeting.
- To explore emerging strategies for overcoming cancer drug resistance.
Main Methods:
- Literature review of dual-target drug development in cancer.
- Analysis of small-molecule compounds targeting specific resistance mechanisms.
- Examination of strategies including mutation resistance, compensatory mechanisms, synthetic lethality, and synergistic effects.
Main Results:
- Dual-target drug development is a promising strategy to improve drug efficiency.
- Small-molecule compounds can effectively target mutation resistance and compensatory pathways.
- Emerging strategies show potential for novel cancer therapeutic approaches.
Conclusions:
- Dual-target drug strategies, particularly with small molecules, offer a path to overcome cancer drug resistance.
- This review highlights key therapeutic approaches for future drug discovery.
- Further research into dual-target drugs can lead to more effective cancer treatments.
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