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Systems pharmacogenomics identifies novel targets and clinically actionable therapeutics for medulloblastoma

Medulloblastoma is the most common malignant paediatric brain tumour and a leading cause of cancer-related mortality and morbidity. Existing treatment protocols are aggressive in nature resulting in significant neurological, intellectual and physical disabilities for the children undergoing treatment. Thus, there is an urgent need for improved, targeted therapies that minimize these harmful side effects.

Veliparib Is an Effective Radiosensitizing Agent in a Preclinical Model of Medulloblastoma

Medulloblastoma is the most common malignant childhood brain tumor, and 5-year overall survival rates are as low as 40% depending on molecular subtype, with new therapies critically important. As radiotherapy and chemotherapy act through the induction of DNA damage, the sensitization of cancer cells through the inhibition of DNA damage repair pathways is a potential therapeutic strategy.

A surveillance clinic for children and adolescents with, or at risk of, hereditary cancer predisposition syndromes

Hereditary cancer predisposition syndromes (HCPS) account for at least 10% of paediatric cancers.1 Li‐Fraumeni syndrome (LFS) is a dominant HCPS caused by mutations in the TP53 gene and is associated with an 80–90% lifetime risk of cancer, commencing in infancy.2 Children of affected individuals are at 50% risk of inheriting the family mutation.

Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma

Medulloblastoma (MB) consists of four core molecular subgroups with distinct clinical features and prognoses. Treatment consists of surgery, followed by radiotherapy and cytotoxic chemotherapy. Despite this intensive approach, outcome remains dismal for patients with certain subtypes of MB, namely, MYC-amplified Group 3 and TP53-mutated SHH. Using high-throughput assays, six human MB cell lines were screened against a library of 3208 unique compounds. We identified 45 effective compounds from the screen and found that cell cycle checkpoint kinase (CHK1/2) inhibition synergistically enhanced the cytotoxic activity of clinically used chemotherapeutics cyclophosphamide, cisplatin, and gemcitabine.

Diffuse Intrinsic Pontine Glioma

This chapter summarizes recent advances in diffuse intrinsic pontine glioma and potential novel therapies

Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult

This study demonstrates that exercise is achievable and has positive effects on vascular function, submaximal fitness, local strength and physical activity in a population of AYA survivors of pediatric oncology related cerebral insult

"Pre-emptive strike"-the case for early treatment of hepatic sinusoidal obstruction syndrome with defibrotide

We describe the case of a child with a right 11th rib primitive neuroectodermal tumor who developed HSOS following focal radiotherapy and actinomycin-D treatment

Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry

These findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma

Activation of ERBB4 in Glioblastoma Can Contribute to Increased Tumorigenicity and Influence Therapeutic Response

Despite low ERBB4 mRNA in glioblastoma, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target

Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma

We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with diffuse intrinsic pontine glioma