Targeting feedback activation of signaling transduction pathways to overcome drug resistance in cancer

• Published in: Drug resistance updates Vol. 65; p. 100884
• Main Authors: Wang, Xuejian, Jiang, Wenyan, Du, Yanmei, Zhu, Dongqi, Zhang, Jian, Fang, Chunyan, Yan, Fang, Chen, Zhe-Sheng
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-12-2022
• Subjects: Cancer; Drug-resistance; Feedback activation; Signaling transduction; Signaling transduction; Feedback activation; Drug-resistance; Cancer
• ISSN: 1368-7646; 1532-2084
• DOI: 10.1016/j.drup.2022.100884

Dysregulation or aberrant signaling transduction contributes to tumorigenesis. Targeting these abnormal signaling pathways becomes an effective anticancer strategy. However, feedback activation or crosstalk between signaling pathways drives adaptive drug resistance which causes failure of cancer therapy. In this review article, we summarized treatments that cause feedback activation of AKT, ERK, STAT3, EGFR, FGFR, and HER2/3 signaling pathways and the combination therapy to enhance anti-tumor effect or to overcome drug resistance, to explore the underlying mechanisms that define the protein molecules participated or regulated the feedback activation. In addition, we reviewed clinical trials that employ combination treatments to suppress feedback activation and improve therapeutic efficacy of cancer treatments.