Molecular Mechanisms Underlying Anthracycline Cardiotoxicity: Challenges in Cardio-Oncology
Bibliographic record
Abstract
The advent of new chemotherapeutic agents has tremendously increased the survival rate of cancer patients. However, the majority, if not all the anticancer therapies in clinical use, is associated with adverse cardiotoxicity, which affects the quality of life of cancer patient survivors. Cardiac arrhythmia, ischemia, pericarditis, and systolic and diastolic dysfunction are the common abnormalities most cancer patient survivors experience for rest of their lives. Chemotherapy is the most common cancer treatment and mainly includes anthracyclines, alkylating agents, antimetabolites, and mitotic and topoisomerase inhibitors (Minami M, Matsumoto S, Horiuchi H. Cardiovascular side-effects of modern cancer therapy. Circ J 2010;74:1779–86). Over the past 3 decades, anthracyclines have been proven as an efficient oncological medication and are among the most widely prescribed drugs used to treat human malignancies (Torti FM, Bristow MM, Lum BL, Carter SK, Howes AE, Aston DA, Brown Jr BW, Hannigan Jr JF, Meyers FJ, Mitchell EP. Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy. Cancer Res 1986;46:3722–27), however, a major consideration includes the associated cardiotoxic effects that limit their usage. Of note, approximately two million people in the USA alone may be at risk of delayed anthracycline toxicity (Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, Avkiran M, de AE, Balligand JL, Brutsaert DL, Condorelli G, Hansen A, Heymans S, Hill JA, Hirsch E, Hilfiker-Kleiner D, Janssens S, de JS, Neubauer G, Pieske B, Ponikowski P, Pirmohamed M, Rauchhaus M, Sawyer D, Sugden PH, Wojta J, Zannad F, Shah AM. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2011;13:1–10). For the effective management of cancer patients it is imperative to reduce or minimize the side effects of anthracyclines on the heart. Therefore, understanding the molecular mechanisms that underlie the cardiotoxic effects of anthracycline and related compounds is of paramount importance in reducing morbidity and mortality in cancer patients treated with these agents. The current literature describing the molecular mechanisms underlying anthracycline cardiomyopathy will be discussed in this chapter.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.005 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".