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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.

Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer

The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations.

RAD51-Mediated DNA Homologous Recombination Is Independent of PTEN Mutational Status

PTEN mutation occurs in a variety of aggressive cancers and is associated with poor patient outcomes. Recent studies have linked mutational loss of PTEN to reduced RAD51 expression and function, a key factor involved in the homologous recombination (HR) pathway. However, these studies remain controversial, as they fail to establish a definitive causal link to RAD51 expression that is PTEN-dependent, while other studies have not been able to recapitulate the relationship between the PTEN expression and the RAD51/HR function.

Challenges to curing primary brain tumours

The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment in brain tumours

The Australian and New Zealand Children's Haematology/Oncology Group Biobanking Network

The ANZCHOG-BN was developed to improve and streamline access to high quality pediatric and adolescent/young adult cancer biospecimens for cancer research

Most clinical anti-EGFR antibodies do not neutralize both wtEGFR and EGFRvIII activation in glioma

We discovered a previously unknown major resistance mechanism in glioma in that most EGFR domain III-targeting antibodies do not neutralize EGFRvIII

International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma

This multi-center study provides valuable information on the success rate of establishing patient-derived pre-clinical models of diffuse intrinsic pontine glioma

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