Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma

We focus on the role of Reactive oxygen species production in PHEO and PGL, predominantly in SDHB-mutated cases

Katerina Hadrava Hadrava Vanova; Chunzhang Yang; Leah Meuter; Jiri Neuzil; Karel Pacak

2021

Scholarcy highlights

  • Reactive oxygen species are oxygen-containing molecules with high reactivity including hydroxyl and superoxide radicals as well as superoxide non-radical molecules such as hydrogen peroxide
  • Antioxidant enzymes closely regulate ROS production based on a scavenging system that is crucial for protecting eukaryotic cells from oxidative damage and other pathological processes including tumorigenesis
  • Cancer cells thrive on slightly higher levels of ROS compared to normal cells, cancer cells are more sensitive to external stimuli, which leads to significant redox adaptation and cell death induction
  • The insignificant findings of this study may be partially explained by the limited number of PHEO/PGL cases and lack of cases with SDHB mutations associated with ROS-mediated anticancer effects as well as by the specificity of certain Tyrosine kinase inhibitors
  • Targeting nuclear factor erythroid-2 related factor 2-dependent GSH synthesis was effective in the metastatic model of SDHB-silenced PHEO/PGL, more strategies to prevent the overall production and/or availability of GSH in tumor cells may be beneficial in future PHEO/PGL therapies
  • Patients with SDHB-mutated PHEO/PGL have a higher likelihood of metastatic disease with limited therapeutic options and poor prognosis
  • All authors have read and agreed to the published version of the manuscript

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