Targeting the Redox Landscape in Cancer Therapy

Narayanan, D.; Ma, Sana; Özcelik, Dennis

doi:10.3390/cancers12071706

Cited by 31 publications

(24 citation statements)

References 296 publications

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“…The redox landscape extends beyond the single cell to the TME. Moreover, the TME is associated with a reduced oxygen concentration, initiating a hypoxic environment that is linked to an amplified tumoral aggressiveness (Narayanan et al, 2020 ). Hypoxia would also influence intercellular communication by varying the release and the uptake of EVs by the cells.…”

Section: Ros and Tumor Microenvironmentmentioning

confidence: 99%

Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress

Olivier

Oliver

Lalier

et al. 2021

Front. Mol. Biosci.

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Glioblastomas (GBM) are the most common primary brain tumor with a median survival of 15 months. A population of cells with stem cell properties (glioblastoma stem cells, GSCs) drives the initiation and progression of GBM and is localized in specialized microenvironments which support their behavior. GBM are characterized as extremely resistant to therapy, resulting in tumor recurrence. Reactive oxygen species (ROS) control the cellular stability by influencing different signaling pathways. Normally, redox systems prevent cell oxidative damage; however, in gliomagenesis, the cellular redox mechanisms are highly impaired. Herein we review the dual nature of the redox status in drug resistance. ROS generation in tumor cells affects the cell cycle and is involved in tumor progression and drug resistance in GBM. However, excess ROS production has been found to induce cell death programs such as apoptosis and autophagy. Since GBM cells have a high metabolic rate and produce high levels of ROS, metabolic adaptation in these cells plays an essential role in resistance to oxidative stress-induced cell death. Finally, the microenvironment with the stromal components participates in the enhancement of the oxidative stress to promote tumor progression and drug resistance.

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Section: Ros and Tumor Microenvironmentmentioning

confidence: 99%

Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress

Olivier

Oliver

Lalier

et al. 2021

Front. Mol. Biosci.

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“…One of the main advantages of fractionation in radiotherapy is indeed reoxygenation, i.e., the possibility to supply oxygen to the surviving, previously hypoxic volumes, between fractions [ 140 , 141 ]. Hypoxia can also be tackled with specific drugs (hypoxia sensitizers), some of them currently in promising clinical trials [ 142 , 143 , 144 , 145 ]. Nevertheless, it remains a negative prognostic factor and a major hindrance to radiotherapy, especially in hypofractionation, when reoxygenation is limited or absent [ 146 , 147 , 148 , 149 ].…”

Section: Hypoxiamentioning

confidence: 99%

Carbon Ion Radiobiology

Tinganelli

Durante

2020

Cancers

114

104

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Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue) and be exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and a reduced oxygen enhancement ratio compared to X-rays. Some radiobiological properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different “drug” in oncology, and may elicit favorable responses such as an increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results.

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“…For example, GSH depletion seems to have a profound effect on cell survival and chemosensitivity by promoting oxidative stress-induced cancer cell death [ 51 ]. Current strategies include inhibition of GSH synthesis by targeting the enzyme γ-glutamylcysteine ligase (GCL) or by interfering with the uptake of cystine (precursor of cysteine) through inhibition of the xCT (also known as x c − or SLC7A11) antiporter system [ 60 , 61 ]. In many studies, it has been shown that compounds inhibiting de novo GSH synthesis, such as buthionine sulphoximine (BSO), NOV-002 and sulphasalazine, exhibit anticancer activity by strongly increasing ROS levels (Table 1) [ 62 , 63 ].…”

Section: Ros and Cancermentioning

confidence: 99%

Targeting Redox Metabolism in Pancreatic Cancer

Hadi

Reyes-Castellanos

Carrier

2021

IJMS

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Cell metabolism is reprogrammed in cancer cells to meet their high bioenergetics and biosynthetic demands. This metabolic reprogramming is accompanied by alterations in redox metabolism, characterized by accumulation of reactive oxygen species (ROS). Elevated production of ROS, mostly by mitochondrial respiration, is counteracted by higher production of antioxidant defenses (mainly glutathione and antioxidant enzymes). Cancer cells are adapted to a high concentration of ROS, which contributes to tumorigenesis, metastasis formation, resistance to therapy and relapse. Frequent genetic alterations observed in pancreatic ductal adenocarcinoma (PDAC) affect KRAS and p53 proteins, which have a role in ROS production and control, respectively. These observations led to the proposal of the use of antioxidants to prevent PDAC development and relapse. In this review, we focus on the therapeutic strategies to further increase ROS level to induce PDAC cell death. Combining the promotion of ROS production and inhibition of antioxidant capacity is a promising avenue for pancreatic cancer therapy in the clinic.

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Targeting the Redox Landscape in Cancer Therapy

Cited by 31 publications

References 296 publications

Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress

Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress

Carbon Ion Radiobiology

Targeting Redox Metabolism in Pancreatic Cancer

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