Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage.

The p53 tumor suppressor protein plays a crucial role in detecting and eliminating various oncogenic threats by promoting processes such as cell cycle arrest, DNA repair, senescence, and apoptosis. UBE4B is essential for negatively regulating p53 during normal conditions and following DNA damage. In previous studies, we demonstrated that UBE4B targets phosphorylated p53 for degradation in response to DNA damage.

Targeting p53 for immune modulation: Exploring its functions in tumor immunity and inflammation.

p53, often referred to as the "guardian of the genome," is a critical regulator of cellular responses to stress. p53 plays a dual role in tumor suppression and immune regulation. In addition to its well-known functions of maintaining genomic stability and inducing apoptosis, p53 orchestrates a complex interaction between innate and adaptive immune responses.

IDH-mutant gliomas in children and adolescents - from biology to clinical trials.

Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors associated with age-distinct incidence. In adults, gliomas are characterized by the presence or absence of mutations in isocitrate dehydrogenase (), with mutated (mIDH) gliomas providing favorable outcomes and avenues for targeted therapy with the emergence of mIDH inhibitors.

Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies.

Pediatric high-grade gliomas (pHGGs) are the most aggressive brain tumors in children, necessitating innovative therapies to improve outcomes. Unlike adult gliomas, recent research reveals that childhood gliomas have distinct biological features, requiring specific treatment strategies. Here, we focused on deciphering unique genetic dependencies specific to childhood gliomas.

Comments and Controversies in Oncology: The Tribulations of Trials Developing ONC201.

Our international team highlights issues with efficacy reports in several studies on DMG with the new drug ONC201.

The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.

Pediatric high-grade gliomas (pHGG) are malignant and usually fatal central nervous system (CNS) WHO Grade 4 tumors. The majority of pHGG consist of diffuse midline gliomas (DMG), H3.3 or H3.

A Pilot Evaluation of an Educational Video to Support Consent to a Pediatric Malignancy Biobank.

The collection of biological specimens is necessary to support basic and translational research. However, the complexity of biobanking introduces numerous ethical issues, particularly regarding informed consent. To evaluate the acceptability and perceived benefits of an educational video facilitating the consent process for the Children's Cancer Centre Biobank.

Lessons learnt in the first year of an Australian pediatric cardio oncology clinic.

Background: Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations for high-risk patients who should be monitored in a pediatric cardio-oncology clinic have previously been developed by expert Delphi consensus by our group. In 2022 we opened our first multidisciplinary pediatric cardio-oncology clinic adhering to these recommendations in surveillance and management.

A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial fused ependymoma.

Background: (formerly known as fused supratentorial ependymoma (fus ST-EPN) has been recognized as a novel entity in the 2016 WHO classification of CNS tumors and further defined in the recent 2021 edition. fus ST-EPN was reported to portend poorer prognosis when compared to its counterpart, ST-EPN in some previously published series. The aim of this study was to determine the treatment outcome of molecularly confirmed and conventionally treated fus ST-EPN patients treated in multiple institutions.

HER2 chimeric antigen receptor T cell immunotherapy is an effective treatment for diffuse intrinsic pontine glioma.

Background: Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMG) of the thalamus and spinal cord are rare but devastating high-grade glial tumors of childhood with no curative treatment. Despite aggressive treatment attempts the prognosis has remained poor. Chimeric antigen receptor (CAR) T cell therapy has been identified as a promising new approach in the treatment of DMG tumors; however, additional targets are urgently required given known tumor heterogeneity and the prospect of antigen escape of this cancer.

ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma.

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG.

BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.

The mitogen-activated protein kinase (MAPK) pathway signaling pathway is one of the most commonly mutated pathways in human cancers. In particular, BRAF alterations result in constitutive activation of the rapidly accelerating fibrosarcoma-extracellular signal-regulated kinase-MAPK significant pathway, leading to cellular proliferation, survival, and dedifferentiation. The role of BRAF mutations in oncogenesis and tumorigenesis has spurred the development of targeted agents, which have been successful in treating many adult cancers.

RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed.

The SWIB/MDM2 motif of UBE4B activates the p53 pathway.

The tumor suppressor p53 plays a critical role in cancer pathogenesis, and regulation of p53 expression is essential for maintaining normal cell growth. UBE4B is an E3/E4 ubiquitin ligase involved in a negative-feedback loop with p53. UBE4B is required for Hdm2-mediated p53 polyubiquitination and degradation.