{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:29:09Z","timestamp":1789615749414,"version":"build-2803163510"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Cyclin\u2010dependent kinase 4\/6 inhibitors have transformed hormone receptor (HR)\u2010positive, human epidermal growth factor receptor 2 (HER2)\u2010negative metastatic breast cancer (BC) therapeutics. Ribociclib has been associated with survival gain, yet its potential cardiovascular toxicities (CVTs) remain an area of uncertainty. Our single\u2010center study prospectively recruited adult patients in order to assess treatment\u2010related CVT incidence and spectrum as well as decipher proteins\u2019 differential expression in affected patients by data\u2010independent acquisition liquid chromatography\u2010tandem mass spectrometry (DIA LC\u2010MS\/MS). After a median follow\u2010up of 27.2\u00a0months, five cases of CVT have occurred among the 62 enrolled participants (8.06%; mean age, 67\u00a0years). CVTs were in the form of asymptomatic QTc prolongation, transient ischemic attack, deep vein thrombosis, syncope, and pericardial effusion, which developed within 7.56\u00a0months. The in\u2010depth proteomics quantified 144 differentially expressed proteins, of which 109 and 35 were down\u2010 and up\u2010regulated, respectively, in these five cases (enrolled participants with CVT) compared to five sex\u2010 and age\u2010matched controls (enrolled participants without CVT). Negative regulation of endopeptidase activity, phosphatidylcholine metabolism, and immune response were the most affected signaling pathways in the subsequent functional analysis. Large\u2010scale external validation of our hypothesis\u2010generating findings could potentially support individualized cardiovascular prevention in BC patients under ribociclib combinational therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Ribociclib has unequivocally revolutionized hormone\u2010dependent metastatic breast cancer therapeutics. Its potential cardiotoxicity, however, remain inadequately characterized, whereas the underlying pathophysiological mechanisms are poorly understood so far.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our prospective case\u2013control study revealed that despite cardiovascular toxicity was not very common (&lt;10%), its phenotype was not limited to QTc prolongation. Moreover, utilizing mass spectrometry\u2010based serum proteomics, we highlighted for the very first time a number of distinct proteins, which could be of predictive value to identify patients at high risk.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The prospective validation of our preliminary, proof\u2010of\u2010concept study's results in larger cohorts could inform optimized preventive strategies.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.70021","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T10:50:58Z","timestamp":1756464658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Proteomics of Ribociclib\u2010Mediated Cardiovascular Toxicity: An Exploratory Case\u2013Control Study"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7106-4162","authenticated-orcid":false,"given":"Oraianthi","family":"Fiste","sequence":"first","affiliation":[{"name":"Department of Clinical Therapeutics &amp; 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