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Molecular Targeted Therapies: Time for a Paradigm Shift in Medulloblastoma Treatment?

ABSTRACT: Medulloblastoma is a rare malignancy of the posterior cranial fossa. Although until now considered a single disease, according to the current WHO classification, it is a heterogeneous tumor that comprises multiple molecularly defined subgroups, with distinct gene expression profiles, pathogenetic driver alterations, clinical behaviors and age at onset. Adult medulloblastoma, in particular, is considered a rarer "orphan" entity in neuro-oncology practice because while treatments have progressively evolved for the pediatric population, no practice-changing prospective, randomized clinical trials have been performed in adults. In this scenario, the toughest challenge is to transfer the advances in cancer genomics into new molecularly targeted therapeutics, to improve the prognosis of this neoplasm and the treatment-related toxicities. Herein, we focus on the recent advances in targeted therapy of medulloblastoma based on the new and deeper knowledge of disease biology.

SUBMITTER: Gatto L

PROVIDER: S-EPMC8773620 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Molecular Targeted Therapies: Time for a Paradigm Shift in Medulloblastoma Treatment?

Gatto Lidia L Franceschi Enrico E Tosoni Alicia A Di Nunno Vincenzo V Bartolini Stefania S Brandes Alba Ariela AA

Cancers 20220111 2

Medulloblastoma is a rare malignancy of the posterior cranial fossa. Although until now considered a single disease, according to the current WHO classification, it is a heterogeneous tumor that comprises multiple molecularly defined subgroups, with distinct gene expression profiles, pathogenetic driver alterations, clinical behaviors and age at onset. Adult medulloblastoma, in particular, is considered a rarer "orphan" entity in neuro-oncology practice because while treatments have progressivel ...[more]

PMID: 35053495

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Project description:ObjectiveOne route to improve adolescent addiction treatment outcomes is to use translational approaches to help identify developmental neuroscience mechanisms that undergird active treatment ingredients and advance adolescent behavior change.MethodsThis sample included 163 adolescents (ages 15-19) randomized to motivational interviewing (MI) vs. brief adolescent mindfulness (BAM). Youth completed an fMRI paradigm assessing adolescent brain response to therapist language (complex reflection vs. mindful; complex reflection vs. confront; mindful vs. confront) at pre- (prior to the completion of the full intervention) and post-treatment (at 3-month follow-up) and behavioral measures at 3, 6 and 12 months.ResultsYouth in both treatment groups showed significant problem drinking reductions at 3 and 6 months, but MI youth demonstrated significantly better treatment outcomes than BAM youth at 12 months. We observed several significant treatment group differences (MI > BAM) in neural response to therapist language, including at pre-treatment when examining complex reflection vs. mindful, and complex reflection vs. confront (e.g., superior temporal gyrus, lingual gyrus); and at post-treatment when examining mindful vs. confront (e.g., supplementary motor area; middle frontal gyrus). When collapsed across treatment groups (MI + BAM), we observed significant differences by time, with youth showing a pattern of brain change in response to complex reflection vs. mindful, and complex reflection vs. confront (e.g., precuneus; postcentral gyrus). There was no evidence of a significant group × time interaction. However, brain change in response to therapist language (complex reflection vs. confront) in regions such as middle frontal gyrus, was associated with reductions in problem drinking at 12 months. Yet, few treatment group differences were observed.ConclusionsThese data underscore the need to better understand therapist language and it's impact on the developing brain, in order to inform and aggregate the most impactful elements of addiction treatment for future treatment development for adolescents.

Dataset Information

Molecular Targeted Therapies: Time for a Paradigm Shift in Medulloblastoma Treatment?

Publications

Molecular Targeted Therapies: Time for a Paradigm Shift in Medulloblastoma Treatment?

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