The complex interconnection between reactive oxygen species (ROS) levels and cancer is based on the precise fine-tuning of ROS production and clearance. The occurrence and progression of cancer leverage a slight increase in ROS levels. Thus, increased intracellular ROS levels and enhanced antioxidant defense systems have been considered as one of the hallmarks of cancer. As a result, two possible ROS-related anticancer treatment strategies emerged. The first strategy is based on inhibiting the ROS production pathway or employing antioxidants to enhance ROS clearance to reduce intracellular ROS levels to counteract their role in cell transformation. This strategy of chemoprevention aims to reduce the number of transformed cells by depriving fuel, thereby protecting normal cells from malignant transformation, and inhibiting early stages of tumorigenesis. The second method is based on that cancer cells, with an already triggered antioxidant system, are more sensitive to further increase in ROS than their normal counterparts, and ultimately fail to achieve intracellular redox balance. This chemotherapy method aims to stimulate intracellular ROS to a toxicity threshold to activate a ROS-induced cell death (apoptosis, necrosis, autophagy, ferroptosis, etc.) pathway.
Another important cellular homeostatic mechanism is autophagy, with important roles in the cellular maintenance, degradation, and secretion. The autophagic process is tightly linked to ROS production since damaged mitochondria are degraded by mitophagy, and modulation of autophagy is a potential mechanism for maintaining mitochondrial fitness and a potential target for cancer therapy.
Targeting redox regulation and autophagy systems or related pathways through biologically active small molecule candidates is considered to be a promising method for cancer therapy. This Research Topic will introduce the currently therapeutic molecules targeting the redox regulation and autophagy systems for cancer therapy, and discuss several challenges in developing cancer therapeutic agents based on ROS or autophagy regulation and propose the direction of future developments.
We welcome Original Research, Review, and Mini-review covering, but not limited to the following subjects:
• Redox-active compounds targeting redox homeostasis or autophagic pathways to induce cell apoptosis, autophagy, DNA damage, and ferroptosis.
• Small molecules capable of modifying ROS levels and potentiating the effect of anticancer drugs.
• Small molecules targeting redox regulation and autophagy, DNA damage systems as drug resistance capable of modifying ROS levels and potentiating the effect of anticancer drugs.
• Redox-active compounds regulating glutathione peroxidase, glutathione, and thioredoxin systems for cancer chemotherapy or chemoprevention.
• Mechanistic study of novel agents that may regulate the ROS homeostasis or induce autophagy for cancer therapy.
• Clinical development and potential of redox-active compounds in cancer therapy.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
The complex interconnection between reactive oxygen species (ROS) levels and cancer is based on the precise fine-tuning of ROS production and clearance. The occurrence and progression of cancer leverage a slight increase in ROS levels. Thus, increased intracellular ROS levels and enhanced antioxidant defense systems have been considered as one of the hallmarks of cancer. As a result, two possible ROS-related anticancer treatment strategies emerged. The first strategy is based on inhibiting the ROS production pathway or employing antioxidants to enhance ROS clearance to reduce intracellular ROS levels to counteract their role in cell transformation. This strategy of chemoprevention aims to reduce the number of transformed cells by depriving fuel, thereby protecting normal cells from malignant transformation, and inhibiting early stages of tumorigenesis. The second method is based on that cancer cells, with an already triggered antioxidant system, are more sensitive to further increase in ROS than their normal counterparts, and ultimately fail to achieve intracellular redox balance. This chemotherapy method aims to stimulate intracellular ROS to a toxicity threshold to activate a ROS-induced cell death (apoptosis, necrosis, autophagy, ferroptosis, etc.) pathway.
Another important cellular homeostatic mechanism is autophagy, with important roles in the cellular maintenance, degradation, and secretion. The autophagic process is tightly linked to ROS production since damaged mitochondria are degraded by mitophagy, and modulation of autophagy is a potential mechanism for maintaining mitochondrial fitness and a potential target for cancer therapy.
Targeting redox regulation and autophagy systems or related pathways through biologically active small molecule candidates is considered to be a promising method for cancer therapy. This Research Topic will introduce the currently therapeutic molecules targeting the redox regulation and autophagy systems for cancer therapy, and discuss several challenges in developing cancer therapeutic agents based on ROS or autophagy regulation and propose the direction of future developments.
We welcome Original Research, Review, and Mini-review covering, but not limited to the following subjects:
• Redox-active compounds targeting redox homeostasis or autophagic pathways to induce cell apoptosis, autophagy, DNA damage, and ferroptosis.
• Small molecules capable of modifying ROS levels and potentiating the effect of anticancer drugs.
• Small molecules targeting redox regulation and autophagy, DNA damage systems as drug resistance capable of modifying ROS levels and potentiating the effect of anticancer drugs.
• Redox-active compounds regulating glutathione peroxidase, glutathione, and thioredoxin systems for cancer chemotherapy or chemoprevention.
• Mechanistic study of novel agents that may regulate the ROS homeostasis or induce autophagy for cancer therapy.
• Clinical development and potential of redox-active compounds in cancer therapy.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
