{"doi":"10.1093/neuonc/noae018","title":"Targeted therapy done right: Direct sonic hedgehog inhibition for sonic hedgehog medulloblastoma","abstract":"Medulloblastoma is the most common malignant brain tumor of childhood and rarely occurs in adulthood.It is subdivided into 4 molecular alterations-based groups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. Standard of care includes maximally safe surgical resection, radiation therapy, and systemic chemotherapy.Very young children (<3 years old) who cannot safely receive craniospinal radiation are treated instead with myeloablative chemotherapy requiring autologous stem cell rescue.Intensive multimodal therapy is curative in approximately 70% of patients, but those who live free of disease incur at least 1 long-term side effect and an increased risk of secondary cancers. 1 As a result, there remains a great need to improve survival and mitigate therapy induced morbidity by developing new treatment approaches.Targeted therapy utilizing the smoothened (SMO) inhibitor, vismodegib, in SHH medulloblastoma has been an active area of research spanning from the bench to bedside. 2 SHH medulloblastoma occurs in young children under 5 years of age and adolescents older than 16 years of age through adulthood.Despite clinical evidence that oral vismodegib benefits a subset of patients with SHH medulloblastoma harboring PTCH1 mutations, its development has been limited to older patients because of irreversible damage to the growth plate and bone development. 3Kresbach et al. evaluated an alternative method of delivering vismodegib via an intraventricular route in genetically engineered infant mice that spontaneously develop medulloblastoma. 4These studies are to be applauded for rigor and quality investigations that will definitely move the field forwards toward diminishing systemic toxicities for CNS tumors.Comparing intraventricular vismodegib to oral vismodegib, they found that intraventricular vismodegib regressed tumor growth (partial or complete) and prolonged rodent model survival.And only oral vismodegib led to bone abnormalities and growth delays.While these findings are very promising, they motivate further immunologic, pharmacokinetic, and toxicity studies for use in young children with SHH medulloblastoma.","journal":"Neuro-Oncology","year":2024,"id":470423,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":470097,"name":"Sadhana Jackson","orcid":"0000-0001-6700-5621","position":1,"is_corresponding":false},{"id":437580,"name":"Anandani Nellan","orcid":"0000-0001-8751-2401","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:05:36.656771Z","pmid":"38290484","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}