Abstract
Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Despite tremendous resources being invested in prevention and treatment for cancer, cancer remains a leading cause of human deaths and brings a heavy burden to humans worldwide. Chemotherapy remains the key treatment for cancer therapy, but it produces harmful side effects. Meanwhile, the process of de novo development of new anticancer drugs generally needs increasing cost, long development cycle, and high risk of failure. The use of ROS-based repurposed drugs may be one of the promising ways to overcome current cancer treatment challenges. In this review, we briefly introduce the source and regulation of ROS and then focus on the status of repurposed drugs based on ROS regulation for cancer therapy and propose the challenges and direction of ROS-mediated cancer treatment.
Highlights
As a common and frequently occurring disease worldwide, cancers increasingly continue to produce serious clinical and socioeconomic issues [1, 2]
Extensive efforts have been made to develop novel and highly efficacious tumortargeting agents [6]. It is the frequent appearance of resistance concomitant with targeted therapies and the higher budgets of targeted drugs that account for the limited use clinically, which lead to the classical cytotoxic drugs to remain the first choice for patients [7, 8]
When cells further adapt to sustained exposure to high reactive oxygen species (ROS) levels, which causes activation of Krüppel-like transcription factor 9 (KLF9) and downregulation of nuclear factor erythroid 2-related factor 2 (NRF2), the NRF2-induced defense cannot counteract the excess ROS, triggering additional redox switches that activate other members of the antioxidant transcription factor network [20] (Figure 4)
Summary
As a common and frequently occurring disease worldwide, cancers increasingly continue to produce serious clinical and socioeconomic issues [1, 2]. Global cancer mortality is not much decreased compared with those in the past decades, though many new anticancer drugs have been approved for tumor prevention or treatment [4]. Extensive efforts have been made to develop novel and highly efficacious tumortargeting agents [6]. It is the frequent appearance of resistance concomitant with targeted therapies and the higher budgets of targeted drugs that account for the limited use clinically, which lead to the classical cytotoxic drugs to remain the first choice for patients [7, 8]. There is still a need to develop more effective and less toxic anticancer drugs worldwide to prevent and treat cancer. Few new anticancer drugs are approved by the FDA annually (Figure 1), though more than 10,000 clinical trials have been completed to evaluate cancer drug
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