Abstract
Central nervous system tumors are the most common pediatric solid tumors and account for 20–25% of all childhood malignancies. Several lines of evidence suggest that brain tumors show altered redox homeostasis that triggers the activation of various survival pathways, leading to disease progression and chemoresistance. Among these pathways, heme oxygenase-1 (HO-1) plays an important role. HO-1 catalyzes the enzymatic degradation of heme with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin. The biological effects of HO-1 in tumor cells have been shown to be cell-specific since, in some tumors, its upregulation promotes cell cycle arrest and cellular death, whereas, in other neoplasms, it is associated with tumor survival and progression. This review focuses on the role of HO-1 in central nervous system malignancies and the possibility of exploiting such a target to improve the outcome of well-established therapeutic regimens. Finally, several studies show that HO-1 overexpression is involved in the development and resistance of brain tumors to chemotherapy and radiotherapy, suggesting the use of HO-1 as an innovative therapeutic target to overcome drug resistance. The following keywords were used to search the literature related to this topic: nuclear factor erythroid 2 p45-related factor 2, heme oxygenase, neuroblastoma, medulloblastoma, meningioma, astrocytoma, oligodendroglioma, glioblastoma multiforme, and gliomas.
Highlights
Malignancies of the central nervous system (CNS) include neoplasia developing in the brain, spinal cord, and sellar region
This review focuses on the role of heme oxygenase-1 (HO-1) in central nervous system malignancies and the possibility of exploiting such a target to improve the outcome of well-established therapeutic regimens
The following keywords were used to search the literature related to this topic: nuclear factor erythroid 2 p45-related factor 2, heme oxygenase, neuroblastoma, medulloblastoma, meningioma, astrocytoma, oligodendroglioma, glioblastoma multiforme, and gliomas
Summary
Malignancies of the central nervous system (CNS) include neoplasia developing in the brain, spinal cord, and sellar region. Heme oxygenase-2 (HO-2), the constitutive isoform, is responsible for most HO activity, whilst HO-1 is induced either by its physiological substrate heme or by various stimuli including hypoxia, inflammation, and oxidative stress [14,15]. HO-1 is significantly increased in various human tumors both in basal condition and during different anticancer therapies contributing, together with its by-products, to the development of a resistant phenotype [20,21,22] In this regard, it is important to take into due account the existence of a link among Nrf, ROS, HO-1, and p53 as the main transcription factor playing a role during cell stress response, senescence, apoptosis, and carcinogenesis [23,24]. According to the latest CNS tumors classification of the World Health Organization (WHO), our study focused on embryonal tumors, meningiomas, and diffuse astrocytic and oligodendroglial tumors [30]
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