AUTHOR=Wang Wanqing , Jiang Kaipeng , Liu Xue , Li Ju , Zhou Wenshuo , Wang Chang , Cui Jiuwei , Liang Tingting 

TITLE=FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1278056

DOI=10.3389/fphar.2023.1278056

ISSN=1663-9812

ABSTRACT=Drug therapy, including chemotherapy, targeted therapy, immunotherapy, and endocrine therapy, stands as the foremost therapeutic approach for contemporary human malignancies. However, increasing drug resistance during antineoplastic therapy has become a substantial barrier to favorable outcomes in cancer patients. To enhance the effectiveness of different cancer therapies, an in-depth understanding of the unique mechanisms underlying tumor drug resistance and the subsequent surmounting of antitumor drug resistance is required. Recently, F-box and WD Repeat Domaincontaining-7 (FBXW7), a recognized tumor suppressor, has been found to be highly associated with tumor therapy resistance. This review provides a comprehensive summary of the underlying mechanisms through which FBXW7 facilitates the development of drug resistance in cancer. Additionally, this review elucidates the role of FBXW7 in therapeutic resistance of various types of human tumors. The strategies and challenges implicated in overcoming tumor therapy resistance by targeting FBXW7 are also discussed.confirmed the important role of F-box and WD Repeat Domain-containing-7 (FBXW7) in the development of tumor resistance(21-25).The ubiquitin-proteasome system (UPS) is the main pathway forprotein degradation in eukaryotic cells (26-28). Autophagy is primarily responsible for the degradation of most long-lived proteins and some cellular organelles(29). The short-lived, misfolded, and damaged proteins degradation is regulated by cascade of three component enzymes of the UPS including ubiquitin activating E1 enzyme, ubiquitin conjugating E2 enzyme and ubiquitin-protein E3 ligase, respectively (30,31). E3 ligase plays a central role in the protein ubiquitination process, where it determines the specificity of a substrate for degradation (30,32). FBXW7 (also known as FBW7 or hCDC4) is a component of the SKP1-CDc53/Cullin-F-box protein complex (SCF-type E3 ubiquitin ligase)(33). As a wellestablished tumor suppressor, FBXW7 is the most frequently mutated member of the human F-box protein family (33,34). We summarize the general mechanism by which FBXW7 is involved in tumor resistance through the available literature and describe the development of FBXW7 resistance in a variety of human tumors. In addition, we discuss the potential clinical applications of targeting FBXW7 in the treatment of tumor resistance. Finally, we highlight the challenges faced in overcoming tumor resistance using FBXW7.