Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy

Yue Li; Long Zhao; Xiao-Feng Li

doi:10.3389/fonc.2021.700407

Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy

Front Oncol. 2021 Jul 29:11:700407. doi: 10.3389/fonc.2021.700407. eCollection 2021.

Authors

Yue Li^{1

2

3}, Long Zhao^{1

3}, Xiao-Feng Li^{1

3}

Affiliations

¹ Department of Nuclear Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
² The First Affiliated Hospital, Jinan University, Guangzhou, China.
³ Department of Nuclear Medicine, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.

Abstract

Hypoxia is an important characteristic of most solid malignancies, and is closely related to tumor prognosis and therapeutic resistance. Hypoxia is one of the most important factors associated with resistance to conventional radiotherapy and chemotherapy. Therapies targeting tumor hypoxia have attracted considerable attention. Hypoxia-activated prodrugs (HAPs) are bioreductive drugs that are selectively activated under hypoxic conditions and that can accurately target the hypoxic regions of solid tumors. Both single-agent and combined use with other drugs have shown promising antitumor effects. In this review, we discuss the mechanism of action and the current preclinical and clinical progress of several of the most widely used HAPs, summarize their existing problems and shortcomings, and discuss future research prospects.

Keywords: AQ4N; EO9; PR-104; SN30000; TH-302; hypoxia; hypoxia-activated prodrugs; tirapazamine.

Publication types

Systematic Review