Novel strategies for targeting the thioredoxin system for cancer therapy

ABSTRACT

Introduction

The thioredoxin system is increasingly recognized as an important executor for maintaining cell redox homeostasis and regulating multiple cell signaling pathways. Targeting this system for cancer treatment has therefore attracted much attention.

Areas covered

The authors focus on providing coverage and emphasizing the strategy of targeting the thioredoxin system to develop anticancer therapeutics in the past five years, especially from the perspective of discovering novel protein functions or new downstream regulatory pathways, and designing new therapeutic reagents. The authors also provide the readers with their expert perspectives for future development.

Expert opinion

The limited pharmacophore of inhibitors and the slow progress of clinical research partially restrict the development of anticancer drugs targeting the thioredoxin system, necessitating thus novel strategies to accelerate the system for treating cancer. Nevertheless, the synergistic targeting of thioredoxin system for cancer therapy is a promising strategy, particularly with regards to chemotherapy resistance and/or sensitization immunotherapy.

KEYWORDS:

• Thioredoxin
• thioredoxin reductase
• cancer therapy
• redox regulation
• strategies

Article highlights

• Targeting the thioredoxin system is an attractive strategy for cancer therapy.

• The mechanism of inhibiting the thioredoxin system to induce cancer cell death is fully summarized.

• Effective strategies for targeting the thioredoxin system to treat cancer are reasonably proposed.

• The future challenges facing the discovery of therapeutic reagents targeting the thioredoxin system are attempted to be pointed out.

• Synergistic targeting thioredoxin system for cancer therapy is promising, especially in chemotherapy resistance or sensitization immunotherapy.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are funded by the National Natural Science Foundation of China (82003779 and 22077055), the Macao Young Scholars Program (AM201926). They are also funded by the Fundamental Research Funds for the Central Universities (Lanzhou University, lzujbky-2020-47).