N-myc mediated translation control is a therapeutic vulnerability in medulloblastoma

Cancer Res. 2022 Oct 20:CAN-22-0945. doi: 10.1158/0008-5472.CAN-22-0945. Online ahead of print. ABSTRACT Deregulation of N-myc is a leading cause of malignant brain tumors in children. To target N-myc-driven medulloblastoma, most research has focused on identifying genomic alterations or on the analysis of the medulloblastoma transcriptome. Here, we have broadly characterized the translatome of medulloblastoma and […]

Safety and efficacy of intraventricular immunovirotherapy with oncolytic HSV-1 for CNS cancers

Clin Cancer Res. 2022 Oct 14:CCR-22-1382. doi: 10.1158/1078-0432.CCR-22-1382. Online ahead of print. ABSTRACT PURPOSE: Oncolytic virotherapy with herpes simplex virus-1 (HSV) has shown promise for treatment of pediatric and adult brain tumors; however, completed and ongoing clinical trials have utilized intratumoral/peritumoral oncolytic HSV (oHSV) inoculation due intraventricular/intrathecal toxicity concerns. Intratumoral delivery requires an invasive neurosurgical […]

Dormant SOX9-positive cells facilitate MYC-driven recurrence of medulloblastoma

Cancer Res. 2022 Oct 11:CAN-22-2108. doi: 10.1158/0008-5472.CAN-22-2108. Online ahead of print. ABSTRACT Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription […]

Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors

J Immunother Cancer. 2022 Sep;10(9):e004450. doi: 10.1136/jitc-2021-004450. ABSTRACT BACKGROUND: Pediatric brain tumors are the leading cause of cancer death in children with an urgent need for innovative therapies. Glypican 2 (GPC2) is a cell surface oncoprotein expressed in neuroblastoma for which targeted immunotherapies have been developed. This work aimed to characterize GPC2 expression in pediatric […]

The long non-coding RNA <em>SPRIGHTLY</em> and its binding partner PTBP1 regulate exon 5 skipping of <em>SMYD3</em> transcripts in group 4 medulloblastomas

Neurooncol Adv. 2022 Aug 2;4(1):vdac120. doi: 10.1093/noajnl/vdac120. eCollection 2022 Jan-Dec. ABSTRACT BACKGROUND: Although some of the regulatory genes, signaling pathways, and gene regulatory networks altered in medulloblastomas (MB) are known, the roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are poorly described. Here we report that the lncRNA SPRIGHTLY (SPRY4-IT1) gene is upregulated in […]

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 […]