FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

Shimin Chen; Jichun Lin; Jiaojiao Zhao; Qian Lin; Jia Liu; Qiang Wang; Ryan Mui; Leina Ma

doi:10.3389/fonc.2023.1147239

FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

Front Oncol. 2023 Mar 14:13:1147239. doi: 10.3389/fonc.2023.1147239. eCollection 2023.

Authors

Shimin Chen^{1

2

3}, Jichun Lin^{1

2

3}, Jiaojiao Zhao^{1

2

3}, Qian Lin¹, Jia Liu⁴, Qiang Wang⁵, Ryan Mui⁶, Leina Ma^{1

2}

Affiliations

¹ Department of Oncology, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao, China.
² Qingdao Cancer Institute, Qingdao, China.
³ School of Basic Medicine, Qingdao University, Qingdao, China.
⁴ Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China.
⁵ Oncology Department, Shandong Second Provincial General Hospital, Jinan, China.
⁶ Department of Gastroenterology, Sparrow Hospital, Lansing, MI, United States.

Abstract

FBXW7 (F-box and WD repeat domain containing 7) is a critical subunit of the Skp1-Cullin1-F-box protein (SCF), acting as an E3 ubiquitin ligase by ubiquitinating targeted protein. Through degradation of its substrates, FBXW7 plays a pivotal role in drug resistance in tumor cells and shows the potential to rescue the sensitivity of cancer cells to drug treatment. This explains why patients with higher FBXW7 levels exhibit higher survival times and more favorable prognosis. Furthermore, FBXW7 has been demonstrated to enhance the efficacy of immunotherapy by targeting the degradation of specific proteins, as compared to the inactivated form of FBXW7. Additionally, other F-box proteins have also shown the ability to conquer drug resistance in certain cancers. Overall, this review aims to explore the function of FBXW7 and its specific effects on drug resistance in cancer cells.

Keywords: E3 ligase; FBXW7; cancer; drug resistance; immunotherapy.

Publication types

Review

Grants and funding

This work was funded by the National Natural Science Foundation of China (grant nos. 81502065, 81672926 and 81972793) and the Natural Science Foundation of Shandong Province, China (ZR2021MC039).