Deciphering Tumorigenesis: Pathophysiological Roles of Reactive Oxygen Species in Glioblastoma

Background. Reactive oxygen species (ROS) play a significant role in activating multiple signaling pathways for cellular proliferation but can be influential in tumorigenesis. We explore how ROS can be used to aid the advances of therapeutic interventions for glioblastoma, a highly aggressive and reoccurring brain cancer. Methods. Over 30 of the most recent and relevant studies were extensively reviewed to determine the significance and implications of ROS in the pathophysiology of glioblastoma. Results. ROS are essential for cell signaling. At low levels, ROS have been seen to promote tumorigenesis by inducing cell proliferation, which indirectly causes the tumor microenvironment to become hypoxic, inducing angiogenesis and decreased drug sensitivity. It can also promote an immunosuppressed environment by enhancing recruitment of immunosuppressive cells, facilitating invasiveness of the tumor stem cells. What is interesting to note here is that when ROS are increased, oxidative stress and cellular distress are initiated in DNA damage that result in the trigger of programmed cell death. However, stem cells of tumor nature might also develop resistance against programmed cell death through various cellular mechanisms. Thus, therapeutics should be delivered to reverse these resistance mechanisms, making them susceptible to ROS. Conclusion. By exploring ROS mechanisms involved in tumorigenesis, innovative therapies could be potentially developed to precisely target glioblastoma stem cells and prolong life expectancy of cancer patients.