Proteomic insights into paediatric cancer: Unravelling molecular signatures and therapeutic opportunities.

Survival rates in some paediatric cancers have improved greatly over recent decades, in part due to the identification of diagnostic, prognostic and predictive molecular signatures, and the development of risk-directed therapies. However, other paediatric cancers have proved difficult to treat, and there is an urgent need to identify novel biomarkers that reveal therapeutic opportunities. The proteome is the total set of expressed proteins present in a cell or tissue at a point in time, and is vastly more dynamic than the genome. Proteomics holds significant promise for cancer research, as proteins are ultimately responsible for cellular phenotype and are the target of most anticancer drugs. Here, we review the discoveries, opportunities and challenges of proteomic analyses in paediatric cancer, with a focus on mass spectrometry (MS)-based approaches. Accelerating incorporation of proteomics into paediatric precision medicine has the potential to improve survival and quality of life for children with cancer.

Late effects and treatment related morbidity associated with treatment of neuroblastoma patients in a tertiary paediatric centre.

BACKGROUND: Survival of neuroblastoma patients has improved over recent decades, but chronic health issues and treatment related late effects cause significant morbidity in survivors. AIMS: We aimed to describe late effects and long-term toxicity in neuroblastoma patients treated at a tertiary, paediatric institution in Australia. METHODS & RESULTS: Patients with neuroblastoma treated primarily at The Children's hospital at Westmead were eligible for inclusion. Retrospective analysis of 65 (45 with high-risk and 20 with non-high-risk disease) neuroblastoma patients were performed via medical record review. Approximately 60% of patients were >5 years from diagnosis and termed the "full effects cohort" who had a range of medical and psychosocial late effects analysed through descriptive means. The remaining 26 patients who had not yet reached 5 years post treatment had audiometry analysis only. Of the 65 patients, 72% were alive at last follow-up. The median length of follow-up was 7 years from diagnosis amongst survivors. Therapy was according to contemporary protocols for neuroblastoma and ranged from standard cytotoxic therapies to intensive multimodal regimens and/or experimental therapy depending on risk group/relapse status. Of the 39 full effects cohort, 85% suffered from at least one late effect. Late effects were common in the endocrine, dental and audiometry domains with 38%, 49% and 72% of patients affected in these areas, respectively. Neuro-cognitive domains were also notably affected with 46% of patients suffering a deficit. Two thirds of survivors were disease free at last follow-up. CONCLUSION: Survivors of high-risk neuroblastoma suffer from a range of chronic illnesses, which lead to morbidity and affect quality of life of survivors.