Challenges and Recent Advances of Novel Chemical Inhibitors in Medulloblastoma Therapy

Maurya, Anand Kumar; Patel, Upendra Kumar; Yadav, Jitendra Kumar; Singh, Virender; Agarwal, Alka

doi:10.1007/978-1-0716-1952-0_13

Cited by 1 publication

(2 citation statements)

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“…As one of the main therapeutic methods for brain tumors, radiotherapy shows potency but always causes severe side effects, especially in the treatment of pediatric brain tumors. For example, in the most common pediatric brain tumor, cerebellar medulloblastoma, radio‐ and chemotherapy will induce cognitive disorders, endocrine dysfunction and ataxia in patients due to cerebellar injury 32,33 . The high proliferation of GNPs in the developing cerebellum makes them sensitive to radiotherapy, 34 and less mature GNs are differentiated to fulfill the physiological functions of the cerebellum as a consequence.…”

Section: Discussionmentioning

confidence: 99%

“…For example, in the most common pediatric brain tumor, cerebellar medulloblastoma, radio‐ and chemotherapy will induce cognitive disorders, endocrine dysfunction and ataxia in patients due to cerebellar injury. 32 , 33 The high proliferation of GNPs in the developing cerebellum makes them sensitive to radiotherapy, 34 and less mature GNs are differentiated to fulfill the physiological functions of the cerebellum as a consequence. Although in early studies it had been found that the injured cerebellum could regenerate in animal models, the mechanisms have not been fully demonstrated.…”

Section: Discussionmentioning

confidence: 99%

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IFN‐γ promotes radioresistant Nestin‐expressing progenitor regeneration in the developing cerebellum by augmenting Shh ligand production

Hu,

Wang,

Gong

et al. 2023

CNS Neurosci Ther

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BackgroundPatients with brain tumors, especially pediatric brain tumors such as cerebellar medulloblastoma, always suffer from the severe side effects of radiotherapy. Regeneration of neural cells in irradiation‐induced cerebellar injury has been reported, but the underlying mechanism remains elusive.MethodsWe established an irradiation‐induced developing cerebellum injury model in neonatal mice. Microarray, KEGG analysis and semi in vivo slice culture were performed for mechanistic study.ResultsNestin‐expressing progenitors (NEPs) but not granule neuron precursors (GNPs) were resistant to irradiation and able to regenerate after irradiation. NEPs underwent less apoptosis but similar DNA damage following irradiation compared with GNPs. Subsequently, they started to proliferate and contributed to granule neurons regeneration dependent on the sonic hedgehog (Shh) pathway. In addition, irradiation increased Shh ligand provided by Purkinje cells. And microglia accumulated in the irradiated cerebellum producing more IFN‐γ, which augmented Shh ligand production to promote NEP proliferation.ConclusionsNEP was radioresistant and regenerative. IFN‐γ was increased post irradiation to upregulate Shh ligand, contributing to NEP regeneration. Our study provides insight into the mechanisms of neural cell regeneration in irradiation injury of the developing cerebellum and will help to develop new therapeutic targets for minimizing the side effects of radiotherapy for brain tumors.

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Section: Discussionmentioning

confidence: 99%