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| Format: | Artículo Open Access |
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Wiley
2025
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| Online Access: | https://onlinelibrary.wiley.com/doi/10.1002/prca.70021 |
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| author | Oraianthi Fiste Martina Samiotaki Efstathios Manios Chrysanthi Trika Christine Ivy Liacos Constantine Dimitrakakis Meletios Athanasios Dimopoulos Maria Gavriatopoulou Flora Zagouri |
| author_facet | Oraianthi Fiste Martina Samiotaki Efstathios Manios Chrysanthi Trika Christine Ivy Liacos Constantine Dimitrakakis Meletios Athanasios Dimopoulos Maria Gavriatopoulou Flora Zagouri Oraianthi Fiste Martina Samiotaki Efstathios Manios Chrysanthi Trika Christine Ivy Liacos Constantine Dimitrakakis Meletios Athanasios Dimopoulos Maria Gavriatopoulou Flora Zagouri |
| collection | Wiley Open Access |
| contents | Serum Proteomics of Ribociclib‐Mediated Cardiovascular Toxicity: An Exploratory Case–Control Study Oraianthi Fiste Martina Samiotaki Efstathios Manios Chrysanthi Trika Christine Ivy Liacos Constantine Dimitrakakis Meletios Athanasios Dimopoulos Maria Gavriatopoulou Flora Zagouri PROTEOMICS – Clinical Applications ABSTRACTCyclin‐dependent kinase 4/6 inhibitors have transformed hormone receptor (HR)‐positive, human epidermal growth factor receptor 2 (HER2)‐negative 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‐center study prospectively recruited adult patients in order to assess treatment‐related CVT incidence and spectrum as well as decipher proteins’ differential expression in affected patients by data‐independent acquisition liquid chromatography‐tandem mass spectrometry (DIA LC‐MS/MS). After a median follow‐up of 27.2 months, five cases of CVT have occurred among the 62 enrolled participants (8.06%; mean age, 67 years). CVTs were in the form of asymptomatic QTc prolongation, transient ischemic attack, deep vein thrombosis, syncope, and pericardial effusion, which developed within 7.56 months. The in‐depth proteomics quantified 144 differentially expressed proteins, of which 109 and 35 were down‐ and up‐regulated, respectively, in these five cases (enrolled participants with CVT) compared to five sex‐ and age‐matched 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‐scale external validation of our hypothesis‐generating findings could potentially support individualized cardiovascular prevention in BC patients under ribociclib combinational therapy.Summary Ribociclib has unequivocally revolutionized hormone‐dependent metastatic breast cancer therapeutics. Its potential cardiotoxicity, however, remain inadequately characterized, whereas the underlying pathophysiological mechanisms are poorly understood so far. Our prospective case–control study revealed that despite cardiovascular toxicity was not very common (<10%), its phenotype was not limited to QTc prolongation. Moreover, utilizing mass spectrometry‐based 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. The prospective validation of our preliminary, proof‐of‐concept study's results in larger cohorts could inform optimized preventive strategies. 10.1002/prca.70021 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/prca.70021 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_prca_70021 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Serum Proteomics of Ribociclib‐Mediated Cardiovascular Toxicity: An Exploratory Case–Control Study Oraianthi Fiste Martina Samiotaki Efstathios Manios Chrysanthi Trika Christine Ivy Liacos Constantine Dimitrakakis Meletios Athanasios Dimopoulos Maria Gavriatopoulou Flora Zagouri PROTEOMICS – Clinical Applications Serum Proteomics of Ribociclib‐Mediated Cardiovascular Toxicity: An Exploratory Case–Control Study Oraianthi Fiste Martina Samiotaki Efstathios Manios Chrysanthi Trika Christine Ivy Liacos Constantine Dimitrakakis Meletios Athanasios Dimopoulos Maria Gavriatopoulou Flora Zagouri PROTEOMICS – Clinical Applications ABSTRACTCyclin‐dependent kinase 4/6 inhibitors have transformed hormone receptor (HR)‐positive, human epidermal growth factor receptor 2 (HER2)‐negative 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‐center study prospectively recruited adult patients in order to assess treatment‐related CVT incidence and spectrum as well as decipher proteins’ differential expression in affected patients by data‐independent acquisition liquid chromatography‐tandem mass spectrometry (DIA LC‐MS/MS). After a median follow‐up of 27.2 months, five cases of CVT have occurred among the 62 enrolled participants (8.06%; mean age, 67 years). CVTs were in the form of asymptomatic QTc prolongation, transient ischemic attack, deep vein thrombosis, syncope, and pericardial effusion, which developed within 7.56 months. The in‐depth proteomics quantified 144 differentially expressed proteins, of which 109 and 35 were down‐ and up‐regulated, respectively, in these five cases (enrolled participants with CVT) compared to five sex‐ and age‐matched 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‐scale external validation of our hypothesis‐generating findings could potentially support individualized cardiovascular prevention in BC patients under ribociclib combinational therapy.Summary Ribociclib has unequivocally revolutionized hormone‐dependent metastatic breast cancer therapeutics. Its potential cardiotoxicity, however, remain inadequately characterized, whereas the underlying pathophysiological mechanisms are poorly understood so far. Our prospective case–control study revealed that despite cardiovascular toxicity was not very common (<10%), its phenotype was not limited to QTc prolongation. Moreover, utilizing mass spectrometry‐based 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. The prospective validation of our preliminary, proof‐of‐concept study's results in larger cohorts could inform optimized preventive strategies. 10.1002/prca.70021 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Serum Proteomics of Ribociclib‐Mediated Cardiovascular Toxicity: An Exploratory Case–Control Study |
| topic | PROTEOMICS – Clinical Applications |
| url | https://onlinelibrary.wiley.com/doi/10.1002/prca.70021 |