Rethinking therapeutic strategies of dual‐target drugs: An update on pharmacological small‐molecule compounds in cancer

• Published in: Medicinal research reviews Vol. 44; no. 6; pp. 2600 - 2623
• Main Authors: Yang, Yiren, Mou, Yi, Wan, Lin‐Xi, Zhu, Shiou, Wang, Guan, Gao, Huiyuan, Liu, Bo
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2024
• Subjects: 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; cancer treatment; dual‐target drug; therapeutic strategy; target mutation resistance; synthetic lethality; compensatory mechanism; small‐molecule compound; synergistic effect
• ISSN: 0198-6325; 1098-1128; 1098-1128
• DOI: 10.1002/med.22057

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.