Diagnóstico do Cancro, terapêuticas e estilo de vida: Estratégias para ultrapassar a Resistência à Quimioterapia e os Efeitos Adversos a Longo Prazo

CD-CORE aims to improve cancer diagnosis, reduce therapy-related toxicity and optimise treatment strategies. The specific objectives are as follows: RL1 – CANCERBIOMARK RL1.1 – Urinary EV Metabolomics: Develop machine learning models to identify metabolic biomarker patterns from urinary extracellular vesicles for early diagnosis of urological cancers with >90% accuracy, validating the diagnostic performance of the identified biomarker panel using an independent patient cohort. RL1.2 – Urinary Microbiome Analysis: Investigate the composition and functionality of the urinary microbiome—including bacteria, archaea, viruses, and fungi - in the pathology of urological cancers. Using cutting-edge shotgun metagenomics, this research aims to identify distinct microbial signatures, metabolic pathways, and microbial-derived metabolites suggestive of risk for urological cancers' development and/or progression. These insights may contribute to novel biomarkers for early detection and microbiome-targeted therapeutic strategies. RL2 – CANCER-TOX RL2.1– Cardiac, Neuronal, and Renal Cytotoxicity and Metabolomic Profiling: This RL will explore the underlying toxic pathways of adverse outcomes by exposing various cell lines (AC16 cardiomyocytes, neuronal SH-SY5Y cells, and HK-2 renal cells) to chemotherapy and targeted drugs used on urological cancers. Cells will be exposed to subtoxic doses, and metabolomic profiling will be utilized to identify early metabolic shifts that may serve as potential biomarkers for early toxicity. RL2.2 – Holistic View of Toxicity of Anticancer Drugs: The Search for Early Toxicity Biomarkers In Vivo: This RL aims to investigate whether pharmacologically relevant doses of chemotherapeutics and targeted drugs used for renal or bladder cancer induce metabolic profile shifts in available fluids, such as urine and blood. These shifts will be correlated with histological and functional damage in vivo to determine if the metabolic changes precede traditional biomarkers of injury and direct heart, brain, or kidneys’ damage. The objective is to explore these metabolic shifts as potential novel biomarkers for damage. RL3 – CANCERTHERAPY RL3.1 – Integrating Drug Repurposing, Lifestyle Interventions, and Patient Perspectives: 1) To conduct a comprehensive systematic literature review of repurposed drugs, nutrition and exercise in cancer treatment. The goal is to assess the strength of existing evidence and evaluate the potential for clinical translation of these interventions. 2) To evaluate the influence of sociocultural factors on treatment adherence; conduct a multidimensional analysis of patient perspectives. This approach has the potential to improve treatment efficacy, reduce side effects, and enhance patient outcomes in cancer care. RL3.2 – Nanoparticle Drug Delivery and In Vivo Assays in Zebrafish Models: 1) Develop functionalised nanoparticles loaded with repurposed drugs. The objective is to target tumour administration for local effect, thereby reducing side effects associated with systemic drug delivery. 2) Characterization of interactions between standard therapies and repurposed drugs. Evaluating reciprocal interactions between drug effects and sleep patterns. RL3.3 – Pre-clinical Rodent Model: Develop an in vivo rodent model to investigate synergistic effects of repurposed drugs and nutrients; evaluate the protective effect of physical activity against cancer and provide a proof of concept.