A Similar Metabolic Profile Between the Failing Myocardium and Tumor Could Provide Alternative Therapeutic Targets in Chemotherapy-Induced Cardiotoxicity
Bibliographic record
Abstract
Chemotherapy-induced cardiotoxicity (CIC) is an emerging clinical problem with significant healthcare costs and no preventative therapies (1, 2).Identifying selective therapeutic targets in CIC is difficult, in part, because the mechanisms of drug toxicity vary between chemotherapeutics.For example, cardiotoxicity can be acute or chronic, transient or permanent, and can affect myocardial contractility, cardiomyocyte conduction or the myocardial vascular system (3).Thus, candidate CIC therapies would need to target many features involved in cardiac dysfunction, and additionally should not prevent chemotherapy-mediated tumor regression.Although most would agree that investing in new therapies that specifically target the tumor, while not affecting other normal tissues, including the heart would be ideal, this approach is currently impractical, as even the most selective cancer therapies have been associated with cardiotoxicity (1).For example, Bcr-Abl kinase is a specific gene fusion that causes chronic myeologenous leukemia (CML) (4), and although Bcr-Abl kinase inhibitors, including imatinib mesylate are effective in treating CML (5), they are also associated with cardiotoxicity in pre-clinical animal studies and patients (6), suggesting that alternative adjuvant therapies that can prevent, limit or improve CIC need to be developed.The most commonly used preventative therapy for CIC is dexrazoxane (7), and although dexrazoxane has shown some benefit in preventing CIC (7), it has also been associated with prevention of chemotherapy-induced tumor regression (8), and increased incidence in the development of certain types of cancer in pediatric patients (9, 10).In addition, current treatment guidelines for patients diagnosed with CIC often result in discontinuation of the chemotherapy (regardless of the tumor responsiveness) and initiation into standard heart failure treatment regimes (which include β-blockers and angiotensin inhibitors) (11).In both options, for either prevention or treatment of CIC, the myocardium appears to have precedence over the tumor, with patients receiving suboptimal care for their cancer.Rather than separating our treatment regime to focus either on heart failure or cancer, an ideal approach would look for common pathways identified in both tissues, with the aim to limit or improve chemotherapy-induced heart failure, but not prevent (or even enhance) chemotherapy-induced tumor regression.In this opinion article,
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".