Coming in from the cold: overcoming the hostile immune microenvironment of medulloblastoma

Genes Dev. 2022 May 1;36(9-10):514-532. doi: 10.1101/gad.349538.122. ABSTRACT Medulloblastoma is an aggressive brain tumor that occurs predominantly in children. Despite intensive therapy, many patients die of the disease, and novel therapies are desperately needed. Although immunotherapy has shown promise in many cancers, the low mutational burden, limited infiltration of immune effector cells, and immune-suppressive microenvironment […]

Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells in a Mouse Model of Group 3 Medulloblastoma Implicating Myeloid Cells as Favorable Immunotherapy Targets

Front Immunol. 2022 Mar 3;13:837013. doi: 10.3389/fimmu.2022.837013. eCollection 2022. ABSTRACT Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment […]

The current landscape of immunotherapy for pediatric brain tumors

Nat Cancer. 2022 Jan;3(1):11-24. doi: 10.1038/s43018-021-00319-0. Epub 2022 Jan 20. ABSTRACT Pediatric central nervous system tumors are the most common solid malignancies in childhood, and aggressive therapy often leads to long-term sequelae in survivors, making these tumors challenging to treat. Immunotherapy has revolutionized prospects for many cancer types in adults, but the intrinsic complexity of […]

Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma

Cancer Res. 2020 Dec 1;80(23):5393-5407. doi: 10.1158/0008-5472.CAN-20-1655. Epub 2020 Oct 12. ABSTRACT Medulloblastoma is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most patients with medulloblastoma receive similar therapies, including […]

Biallelic loss of <em>GNAS</em> in a patient with pediatric medulloblastoma

Cold Spring Harb Mol Case Stud. 2019 Oct 23;5(5):a004572. doi: 10.1101/mcs.a004572. Print 2019 Oct. ABSTRACT Genome sequencing was performed on matched normal and tumor tissue from a 6.5-yr-old boy with a diagnosis of recurrent medulloblastoma. A pathogenic heterozygous c.432+1G>A canonical splice donor site variant in GNAS was detected on analysis of blood DNA. Analysis of […]

Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma

Sci Signal. 2018 Sep 11;11(547):eaau5147. doi: 10.1126/scisignal.aau5147. ABSTRACT A major limitation of targeted cancer therapy is the rapid emergence of drug resistance, which often arises through mutations at or downstream of the drug target or through intrinsic resistance of subpopulations of tumor cells. Medulloblastoma (MB), the most common pediatric brain tumor, is no exception, and […]