Targeted therapy based on ubiquitin-specific proteases, signalling pathways and E3 ligases in non-small-cell lung cancer

Yu-Chen Yang; Can-Jun Zhao; Zhao-Feng Jin; Jin Zheng; Li-Tian Ma

doi:10.3389/fonc.2023.1120828

Targeted therapy based on ubiquitin-specific proteases, signalling pathways and E3 ligases in non-small-cell lung cancer

Front Oncol. 2023 Mar 9:13:1120828. doi: 10.3389/fonc.2023.1120828. eCollection 2023.

Authors

Yu-Chen Yang¹, Can-Jun Zhao¹, Zhao-Feng Jin², Jin Zheng¹, Li-Tian Ma^{1

3}

Affiliations

¹ Department of Traditional Chinese Medicine, Tangdu Hospital, Air Force Medical University, Xi'an, China.
² School of Psychology, Weifang Medical University, Weifang, China.
³ Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xi'an, China.

Abstract

Lung cancer is one of the most common malignant tumours worldwide, with the highest mortality rate. Approximately 1.6 million deaths owing to lung cancer are reported annually; of which, 85% of deaths occur owing to non-small-cell lung cancer (NSCLC). At present, the conventional treatment methods for NSCLC include radiotherapy, chemotherapy, targeted therapy and surgery. However, drug resistance and tumour invasion or metastasis often lead to treatment failure. The ubiquitin-proteasome pathway (UPP) plays an important role in the occurrence and development of tumours. Upregulation or inhibition of proteins or enzymes involved in UPP can promote or inhibit the occurrence and development of tumours, respectively. As regulators of UPP, ubiquitin-specific proteases (USPs) primarily inhibit the degradation of target proteins by proteasomes through deubiquitination and hence play a carcinogenic or anticancer role. This review focuses on the role of USPs in the occurrence and development of NSCLC and the potential of corresponding targeted drugs, PROTACs and small-molecule inhibitors in the treatment of NSCLC.

Keywords: E3 ligase; NSCLC; PROTACs; USPs; signalling pathway.

Publication types

Review

Grants and funding

Key clinical research projects of the Second Affiliated Hospital of Air Force Military Medical University (2021LCYJ016 to JZ) and Social Talent Fund Funding Program Project (2021SHRC044 to C-JZ).