Rethinking therapeutic strategies of dual-target drugs: An update on pharmacological small-molecule compounds in cancer
Yiren Yang
Department 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
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
Search for more papers by this authorYi Mou
Department 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
Search for more papers by this authorLin-Xi Wan
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
Search for more papers by this authorShiou Zhu
Department 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
Search for more papers by this authorCorresponding Author
Guan Wang
Department 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
Correspondence Guan Wang and Bo Liu, Department 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, 610041, China.
Email: [email protected] and [email protected]
Huiyuan Gao, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Huiyuan Gao
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
Correspondence Guan Wang and Bo Liu, Department 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, 610041, China.
Email: [email protected] and [email protected]
Huiyuan Gao, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Bo Liu
Department 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
Correspondence Guan Wang and Bo Liu, Department 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, 610041, China.
Email: [email protected] and [email protected]
Huiyuan Gao, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Email: [email protected]
Search for more papers by this authorYiren Yang
Department 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
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
Search for more papers by this authorYi Mou
Department 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
Search for more papers by this authorLin-Xi Wan
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
Search for more papers by this authorShiou Zhu
Department 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
Search for more papers by this authorCorresponding Author
Guan Wang
Department 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
Correspondence Guan Wang and Bo Liu, Department 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, 610041, China.
Email: [email protected] and [email protected]
Huiyuan Gao, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Huiyuan Gao
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
Correspondence Guan Wang and Bo Liu, Department 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, 610041, China.
Email: [email protected] and [email protected]
Huiyuan Gao, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Bo Liu
Department 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
Correspondence Guan Wang and Bo Liu, Department 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, 610041, China.
Email: [email protected] and [email protected]
Huiyuan Gao, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Email: [email protected]
Search for more papers by this authorYiren Yang, Yi Mou, and Lin-Xi Wan are contributed equally to this study.
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.
Open Research
DATA AVAILABILITY STATEMENT
All relevant data are within the paper.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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