Adult medulloblastoma: an overview on current and future strategies of treatment

Capozza, Michele Antonio; Trombatore, Giovanna; Triarico, Silvia; Attinà, Giorgio; Maurizi, Palma; Ruggiero, Antonio

doi:10.1080/21678707.2019.1663170

Cited by 2 publications

(2 citation statements)

References 83 publications

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“…In the previous WHO guidelines large cell and anaplastic histology were classified separately, however, large cell medulloblastomas mostly also show anaplastic features, which is why these types were grouped together [ 13 , 15 , 16 ]. Nodular/desmoplastic histology was described to occur more frequently in adults and is associated with a lower risk classification than classic or anaplastic types in both age groups [ 17 ]. Additionally, with the development of genetic and molecular analysis, new subgroups have been defined in the last decade.…”

Section: Medulloblastomamentioning

confidence: 99%

Typical Pediatric Brain Tumors Occurring in Adults—Differences in Management and Outcome

2021

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Adult brain tumors mostly distinguish themselves from their pediatric counterparts. However, some typical pediatric brain tumors also occur in adults. The aim of this review is to describe the differences between classification, treatment, and outcome of medulloblastoma, pilocytic astrocytoma, and craniopharyngioma in adults and children. Medulloblastoma is a WHO IV posterior fossa tumor, divided into four different molecular subgroups, namely sonic hedgehog (SHH), wingless (WNT), Group 3, and Group 4. They show a different age-specific distribution, creating specific outcome patterns, with a 5-year overall survival of 25–83% in adults and 50–90% in children. Pilocytic astrocytoma, a WHO I tumor, mostly found in the supratentorial brain in adults, occurs in the cerebellum in children. Complete resection improves prognosis, and 5-year overall survival is around 85% in adults and >90% in children. Craniopharyngioma typically occurs in the sellar compartment leading to endocrine or visual field deficits by invasion of the surrounding structures. Treatment aims for a gross total resection in adults, while in children, preservation of the hypothalamus is of paramount importance to ensure endocrine development during puberty. Five-year overall survival is approximately 90%. Most treatment regimens for these tumors stem from pediatric trials and are translated to adults. Treatment is warranted in an interdisciplinary setting specialized in pediatric and adult brain tumors.

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Section: Medulloblastomamentioning

confidence: 99%

Typical Pediatric Brain Tumors Occurring in Adults—Differences in Management and Outcome

2021

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“…Historically, MB is divided into four distinct molecular subgroups, namely: wingless (WNT), Sonic hedgehog (SHH), group 3 and group 4 4 . Among which, the SHH contains 30% of all MB diagnosis and is the most studied MB subgroup 5 . The SHH MB is characterized by the somatic mutations in the SHH pathway genes ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Development of hedgehog pathway inhibitors by epigenetically targeting GLI through BET bromodomain for the treatment of medulloblastoma

Liu

Wang

et al. 2021

Acta Pharmaceutica Sinica B

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Medulloblastoma (MB) is a common yet highly heterogeneous childhood malignant brain tumor, however, clinically effective molecular targeted therapy is lacking. Modulation of hedgehog (HH) signaling by epigenetically targeting the transcriptional factors GLI through bromodomain-containing protein 4 (BRD4) has recently spurred new interest as potential treatment of HH-driven MB. Through screening of current clinical BRD4 inhibitors for their inhibitory potency against glioma-associated oncogene homolog (GLI) protein, the BRD4 inhibitor 2 was selected as the lead for further structural optimization, which led to the identification of compounds 25 and 35 as the high potency HH inhibitors. Mechanism profiling showed that both compounds suppressed HH signaling by interacting with the transcriptional factor GLI, and were equally potent against the clinical resistant mutants and the wild type of smoothened (SMO) receptor with IC 50 values around 1 nmol/L. In the resistant MB allograft mice, compound 25 was well tolerated and markedly suppressed tumor growth at both 5 mg/kg (TGI = 83.3%) and 10 mg/kg (TGI = 87.6%) doses. Although further modification is needed to improve the pharmacokinetic (PK) parameters, compound 25 represents an efficacious lead compound of GLI inhibitors, possessing optimal safety and tolerance to fight against HH-driven MB.

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Adult medulloblastoma: an overview on current and future strategies of treatment

Cited by 2 publications

References 83 publications

Typical Pediatric Brain Tumors Occurring in Adults—Differences in Management and Outcome

Typical Pediatric Brain Tumors Occurring in Adults—Differences in Management and Outcome

Development of hedgehog pathway inhibitors by epigenetically targeting GLI through BET bromodomain for the treatment of medulloblastoma

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