Rethinking therapeutic strategies of dual‐target drugs: An update on pharmacological small‐molecule compounds in cancer
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...
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| Published in | Medicinal research reviews Vol. 44; no. 6; pp. 2600 - 2623 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Wiley Subscription Services, Inc
01.11.2024
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| 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. |
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| AbstractList | 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. 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. 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.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. |
| Author | Wang, Guan Liu, Bo Zhu, Shiou Mou, Yi Wan, Lin‐Xi Gao, Huiyuan Yang, Yiren |
| Author_xml | – sequence: 1 givenname: Yiren surname: Yang fullname: Yang, Yiren organization: Shenyang Pharmaceutical University – sequence: 2 givenname: Yi surname: Mou fullname: Mou, Yi organization: Sichuan University – sequence: 3 givenname: Lin‐Xi surname: Wan fullname: Wan, Lin‐Xi organization: Sichuan University – sequence: 4 givenname: Shiou surname: Zhu fullname: Zhu, Shiou organization: Sichuan University – sequence: 5 givenname: Guan surname: Wang fullname: Wang, Guan email: guan8079@163.com organization: Sichuan University – sequence: 6 givenname: Huiyuan surname: Gao fullname: Gao, Huiyuan email: sypugaohy@163.com organization: Shenyang Pharmaceutical University – sequence: 7 givenname: Bo orcidid: 0000-0003-3900-9486 surname: Liu fullname: Liu, Bo email: liubo2400@163.com organization: Sichuan University |
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| Keywords | cancer treatment dual‐target drug therapeutic strategy target mutation resistance synthetic lethality compensatory mechanism small‐molecule compound synergistic effect |
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| Snippet | Oncogenes and tumor suppressors are well‐known to orchestrate several signaling cascades, regulate extracellular and intracellular stimuli, and ultimately... Oncogenes and tumor suppressors are well-known to orchestrate several signaling cascades, regulate extracellular and intracellular stimuli, and ultimately... Abstract Oncogenes and tumor suppressors are well‐known to orchestrate several signaling cascades, regulate extracellular and intracellular stimuli, and... |
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| SubjectTerms | Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Cancer therapies cancer treatment compensatory mechanism Drug Resistance, Neoplasm - drug effects dual‐target drug Humans Molecular Targeted Therapy Mutation Neoplasms - drug therapy Small Molecule Libraries - chemistry Small Molecule Libraries - pharmacology small‐molecule compound synergistic effect synthetic lethality target mutation resistance therapeutic strategy |
| Title | Rethinking therapeutic strategies of dual‐target drugs: An update on pharmacological small‐molecule compounds in cancer |
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