Periodic Reporting for period 3 - SECRETE-HF (SECRETED FACTORS IN CARDIAC REMODELING PROVOKE TUMORIGENESIS AND END ORGAN DAMAGE IN HEART FAILURE)
Periodo di rendicontazione: 2022-09-01 al 2024-02-29
Heart failure and cancer represent global health burdens and are the leading causes of mortality. The ‘modern face’ of heart failure has shifted from single organ failure to multi-organ dysfunction with a higher prevalence of non-cardiac mortality. Epidemiological data reveal that heart failure patients exhibit higher cancer prevalence and mortality rates. The mechanisms behind this phenomenon remain not fully comprehended and require further explorations. Moreover, the co-occurrence of cancer and heart failure imposes significant clinical challenges as each syndrome affects the treatment and management of the other. SECRETE-HF interprets the heart as an endocrine organ and aims to elucidate the systemic effects of the factors secreted by failing hearts on other organs and tumors.
The translational approach adopted by SECRETE-HF from preclinical research to human validation will help to translate our findings into clinical practice by establishing algorithms and clinical prediction models. Consequently, a risk-stratification strategy could be applied to identify predisposed patients. Also, this would pave the way for innovative therapeutic guidelines for HF and its comorbidities, namely organ failure, and cancer, resulting in a better quality of life in these patients.
Overall objectives: SECRETE-HF aims to develop and optimize experimental models to mimic the human situation and allow an accurate evaluation of the mechanisms by which heart failure induces cancer. Preclinical models are designed to demonstrate different combinations of heart failure etiologies and several types of cancer, and are investigated in SECRETE-HF to represent complications faced by humans with both diseases. State-of-the-art unbiased approaches are adopted to identify the cardiac secreted factors from failing hearts. These factors are evaluated for their effect on tumor growth and organ failure. These discoveries are validated first in tumor cells, then in independent in vivo models, and ultimately in human cohorts, with data on incident cancer, cardiovascular disease, and organ function. Finally, SECRETE-HF will establish clinical algorithms using identified cardiac-secreted factors to detect, monitor, and act on extracardiac diseases, namely cancer, and organ failure.
The translational approach adopted by SECRETE-HF from preclinical research to human validation will help to translate our findings into clinical practice by establishing algorithms and clinical prediction models. Consequently, a risk-stratification strategy could be applied to identify predisposed patients. Also, this would pave the way for innovative therapeutic guidelines for HF and its comorbidities, namely organ failure, and cancer, resulting in a better quality of life in these patients.
Overall objectives: SECRETE-HF aims to develop and optimize experimental models to mimic the human situation and allow an accurate evaluation of the mechanisms by which heart failure induces cancer. Preclinical models are designed to demonstrate different combinations of heart failure etiologies and several types of cancer, and are investigated in SECRETE-HF to represent complications faced by humans with both diseases. State-of-the-art unbiased approaches are adopted to identify the cardiac secreted factors from failing hearts. These factors are evaluated for their effect on tumor growth and organ failure. These discoveries are validated first in tumor cells, then in independent in vivo models, and ultimately in human cohorts, with data on incident cancer, cardiovascular disease, and organ function. Finally, SECRETE-HF will establish clinical algorithms using identified cardiac-secreted factors to detect, monitor, and act on extracardiac diseases, namely cancer, and organ failure.
We studied preclinical models representing combinations of heart failure etiologies and cancer types. Currently, additional models are being validated, and potential treatments are being tested in these preclinical models.
By adopting unbiased approaches, libraries of cardiac secreted factors are being prepared from different heart failure etiologies. Our recent data revealed that established tumor biomarkers demonstrated independent associations with the severity of heart failure and other cardiovascular outcomes.
By adopting unbiased approaches, libraries of cardiac secreted factors are being prepared from different heart failure etiologies. Our recent data revealed that established tumor biomarkers demonstrated independent associations with the severity of heart failure and other cardiovascular outcomes.
Our data support the link between heart failure and cancer risk and the notion that cancer and heart failure have similar biological mechanisms. We expect that the SECRETE-HF work will provide deep insights into the interplay between the two syndromes.