We have comprehensively characterized the progression of anthracycline-induced cardiotoxicity in mouse and pig models from anatomical, functional, molecular, and metabolic perspectives. These studies have enabled the identification of early and reversible mitochondrial abnormalities, establishing mitochondrial fragmentation and metabolic dysfunction as central hallmarks of CTiCT.We demonstrated how pressure overload and anthracycline exposure synergistically induce cardiotoxicity, providing mechanistic support for the “dual-hit” concept. We also used novel gene therapy approaches to explore gain- and loss-of-function of key regulators of mitochondrial dynamics, revealing new biological roles for classical mitochondrial proteases. Complementary nutritional strategies—such as high-protein diet—were identified as means to reverse cardiac atrophy and metabolic derangement.
In humans, MATRIX study, have prospectively assessed the incidence, temporal evolution, and predictors of antracyclines related cardiac dysfunction through comprehensive multimodality imaging and biomarker monitoring in lymphoma patients. The results are currently under review for publication.
One of the most relevant outputs of MATRIX is the identification of Remote Ischemic Conditioning (RIPC) as the first mitochondria-targeted, translatable therapy for CTiCT. After demonstrating its strong protective effect in preclinical models and human imaging studies, this intervention was tested in patients in a multicenter clinical trial.
We have developed novel CMR methodologies—including the ultrafast 3D sequence ESSOS—to better detect tissue changes during CTiCT and to make cardiac MRI more accessible to vulnerable oncology populations.
We have optimized protocols to preserve functional mitochondria ex vivo prior to transplantation and have completed a large-animal preclinical trial in pigs demonstrating that intracoronary mitochondrial transplantation after chronic doxorubicin injury leads to cardiac engraftment and functional left ventricular improvement.
Dissemination: Between 2019 and 2025, CNIC’s cardio-oncology research achieved remarkable media visibility at both national and international levels. The dissemination focused on advances in preventing and treating cardiotoxicity associated with cancer therapies, highlighting projects such as MATRIX and RESILENCE, and featuring CNIC’s leadership in European collaborative research. Overall, the coverage reached an estimated audience of several tens of millions, consolidating CNIC’s position as a key reference in cardiovascular research and translational medicine.
A total of approximately 95 media pieces were identified between 2019 and 2025, covering CNIC’s research on cardio-oncology and related topics.
