Desenvolvimento de uma Nova Terapia Protectora Contra a Toxicidade Cardíaca de Tratamentos Anticancerígenos

InSync is an interdisciplinary proposal strategically poised to address pressing challenges in cardiooncology, namely anthracycline-induced cardiotoxicity. Our overarching goal is to develop and pre-clinically validate a pharmaceutical strategy that precisely targets metabolic nodal points, mitigating the cardiac repercussions of anti-cancer treatment, namely those caused by anthracyclines. Sequential events underlying delayed cardiomyopathies triggered by anthracycline treatment will be target to provide a full protection a condition that can affect cancer survivors worldwide. We focus on targeting disrupted mitochondrial respiratory chain function, diminished pyrimidine nucleotide synthesis, ensuing p53 activation, and persistent circadian gene expression alterations. Our objectives are ambitious and go well beyond the state of the art providing a new therapeutic concept to deal with a key objective in cardiooncology. Our specific objectives are: a. Innovation in Therapy Development: novel therapeutic strategy—employing a combinatory approach with novel Mitochondria-Targeted Agents (MTAs) and modulators of pyrimidine production/energy metabolism. This strategy targets the disruption of the mitochondrial respiratory chain (MRC) and downstream events, curtailing cardiac toxicity while preserving the anti-cancer efficacy of anthracyclines. b. Biomarker Discovery: Identify a minimal set of mitochondrial biomarkers with predictive power for in vitro and in vivo DOX cardiotoxicity. Leverage Machine Learning (ML) and bioinformatic tools to distill meaningful insights from extensive datasets, facilitating pre-clinical testing of interventions. c. Advancing Diagnostic Technologies: Validate the in vivo utility of mid-range infrared spectroscopy, leveraging the unique MIRA mid-range IR reader in Portugal. This innovative approach builds a plasma chemical fingerprint to predict cardiotoxicity, transcending conventional diagnostic boundaries. d. Human Resource Development: Contribute to the specialized workforce in cardiooncology. Through advanced training methodologies—courses, workshops, and Master/Doctoral laboratory training—nurture graduate students, post-docs, and project leaders, culminating in impactful theses. e. Communication and Dissemination: Foster open science values by disseminating project results effectively across diverse audiences. From scientific communities to the broader society, we will use open repositories, high-impact publications (three expected), and active participation in national (one) and international (eleven) scientific meetings. Engage stakeholders—oncologists, cardiologists, and society at large—to amplify our reach. f. Value Creation through Intellectual Property: Drive value creation by patenting the final formulation. Our aim is to license this groundbreaking solution to potential partners, cultivating collaborative agreements. MitoTAG, a University of Porto/Coimbra spin-off specializing in mitochondrial therapies, stands as a potential collaborator, charting the course for pre-clinical and clinical validation. The Timeline file contains the full list of "Deliverables" of InSync. g. Roadmap for Future Therapeutic Frontiers: Propel forward by crafting a roadmap for developing therapeutic strategies to combat cardiac aging. Focused on mitochondrial disruption, loss of pyridine nucleotide synthesis, and local circadian regulation, this initiative lays the groundwork for a broader impact.