Infraestructura de Medicina de Precisión asociada a la Ciencia y la Tecnología
Despite the great success achieved in recent years in the treatment of cancer, the persistent cardiotoxic side effects of antitumor therapies continue to be an important cause of morbidity and mortality in cancer survivors, and can develop acutely during treatment, or even years later. Early identification of the mechanisms responsible for cardiovascular damage resulting from the short- and long-term administration of antitumor agents is essential to prevent damage and improve cardiovascular diagnosis in cancer patients.
Currently, some clinical and epidemiological factors are known that predispose to the development of cardiotoxicity, but there are also risk biomarkers and some studies have identified genomic variants that could be associated with cardiotoxicity, as well as other markers related to the inflammatory response or cell metabolism. However, the lack of validation of these factors has limited their translation to clinical practice. Cardiotox-PMP aims to implement the use of risk estimates based on clinical, epidemiological, genomic and biochemical factors, which in combination improve the personalized diagnosis of cancer patients and help the development of new tools for the prevention of cardiovascular complications.
The main objective of this project is to predict the risk of developing anticancer-induced cardiotoxicity, enabling clinical and preventive decision-making to reduce its incidence and reduce or prevent associated adverse cardiovascular outcomes. To this end, we propose:
1- Use the CARDIOTOX registry and biobank to:
1.1- Identify and validate previously described cardiotoxicity risk markers in both sexes (clinical, epidemiological, imaging and biomarkers).
1.2- Identify and quantify new biomarkers (myocardial damage, inflammation biomarkers, Klotho protein and FGB23) susceptible to cardiovascular risk after antitumor treatment, considering sex differences.
1.3- Identify and validate a polygenic risk (PRS) estimate of cardiotoxicity in different sexes, considering common and rare variants.
1.4- Explore risk scores in both sexes that combine clinical parameters, ECG, echocardiography, biomarkers and genetic profiles to predict the risk of toxicity.
2- Define the simplest risk algorithm to predict the presence or absence of cardiac toxicity during follow-up, taking into account the gender perspective.
Social Impact: It is well known that cancer survivors generally have a 2- to 7-fold increased risk of dying from cardiovascular disease compared to the general population. Developing strategies that allow for rapid identification of cardiovascular events related to cancer, and specifically to its treatment, will improve overall prognosis. Cardiotox-PMP aims to develop clinically useful tools to identify the population at risk of developing cardiotoxicity and facilitate the development of strategies aimed at limiting the cardiovascular consequences associated with cancer and its therapy.
Clinical impact: In general, to optimize risk and avoid cardiotoxicity, it is necessary to implement programs for prevention, early detection, and treatment of cardiovascular complications, and, above all, to avoid interruption of oncohematological treatment. Cardiotox-PMP aims to develop a dynamic score related to the risk of cardiotoxicity. This will result, on the one hand, in the early identification of cardiotoxicity and strategies to limit it and, on the other, enable a more comprehensive oncological therapeutic strategy without necessarily discontinuing treatments that have proven effective in cancer.
Economic impact: Personalized precision medicine is clearly aimed at prevention and, therefore, at predicting each patient’s risk, helping to implement appropriate therapeutic measures. These measures include lifestyle recommendations, such as exercise or diet, which do not result in increased costs for the healthcare system but, on the contrary, reduce the need for additional consultations. Early risk detection allows the healthcare system to implement therapeutic measures that, in addition to their health and social impact, will have an undeniable economic impact by reducing costs related to the development of cardiovascular diseases in these patients, as well as promoting more efficient cancer treatment.