Project description:Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed.
Project description:BackgroundPatients with primary brain tumours (i.e., neuro-oncology patients) lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise - Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness.MethodsNeuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro and other cancer rehabilitation services (including physiatry, physiotherapy, occupational therapy, and exercise physiology). In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes and functional fitness, and objective physical activity tracked across the 12-week program. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching.ConclusionWe are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.
Project description:Vaccination against cancer-associated antigens has long held the promise of inducting potent antitumor immunity, targeted cytotoxicity while sparing normal tissues, and long-lasting immunologic memory that can provide surveillance against tumor recurrence. Evaluation of vaccination strategies in preclinical brain tumor models has borne out the capacity for the immune system to effectively and safely eradicate established tumors within the central nervous system. Early phase clinical trials have established the feasibility, safety, and immunogenicity of several vaccine platforms, predominantly in patients with glioblastoma. Definitive demonstration of clinical benefit awaits further study, but initial results have been encouraging. With increased understanding of the stimulatory and regulatory pathways that govern immunologic responses and the enhanced capacity to identify novel antigenic targets using genomic interrogation of tumor cells, vaccination platforms for patients with malignant brain tumors are advancing with increasing personalized complexity and integration into combinatorial treatment paradigms.
Project description:Recent reports herald important advances in our understanding and management of gliomas. A role for alkylator chemotherapy in the management of certain high-grade gliomas has been confirmed and linked to specific, clinically ascertainable molecular markers. Magnetic resonance spectroscopy can now image 2-hydroxyglutarate, an oncometabolite restricted to the three-quarters of low-intermediate grade gliomas harboring an isocitrate dehydrogenase gene mutation; this has powerful implications for diagnosis and assessment of response to therapies. Genome-wide association studies point to several SNPs conveying increased risk of glioma; further studies of the involved genes and RNA products will enhance our understanding of glioma development. Finally, high-throughput sequencing has identified novel mutations in a histone-coding gene and in genes related to the histone complex in pediatric glioblastoma.
Project description:One of the biggest challenges in neuro-oncology is understanding the complexity of central nervous system tumors, such as gliomas, in order to develop suitable therapeutics. Conventional therapies in malignant gliomas reconcile surgery and radiotherapy with the use of chemotherapeutic options such as temozolomide, chloroethyl nitrosoureas and the combination therapy of procarbazine, lomustine and vincristine. With the unraveling of deregulated cancer cell signaling pathways, targeted therapies have been developed. The most affected signaling pathways in glioma cells involve tyrosine kinase receptors and their downstream pathways, such as the phosphatidylinositol 3-kinases (PI3K/AKT/mTOR) and mitogen-activated protein kinase pathways (MAPK). MAPK pathway inhibitors include farnesyl transferase inhibitors, Ras kinase inhibitors and mitogen-activated protein extracellular regulated kinase (MEK) inhibitors, while PI3K/AKT/mTOR pathway inhibitors are divided into pan-inhibitors, PI3K/mTOR dual inhibitors and AKT inhibitors. The relevance of the immune system in carcinogenesis has led to the development of immunotherapy, through vaccination, blocking of immune checkpoints, oncolytic viruses, and adoptive immunotherapy using chimeric antigen receptor T cells. In this article we provide a comprehensive review of the signaling pathways underlying malignant transformation, the therapies currently used in the treatment of malignant gliomas and further explore therapies under development, including several ongoing clinical trials.