Anthracycline Cardiotoxicity as Multicellular Network Failure: Cardiac Niche Reprogramming and Pathological Cell–Cell Communication
- 1The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital
- 2Henan Province Engineering Research Center for Ultrasound‐Targeted Nanomaterials and Minimally Invasive Interventional Technology
Abstract
Anthracyclines are essential anticancer agents, yet a cardiomyocyte‐centered model incompletely explains why cardiac injury can be delayed, progressive, and poorly captured by resting ejection fraction. We frame anthracycline cardiotoxicity as a multicellular network failure within the cardiac niche: the spatially organized interactions among cardiomyocytes, fibroblasts, endothelial and immune cells, extracellular matrix, and circulating signals. Cardiomyocyte stress initiates injury, whereas pathological communication may propagate it. We distinguish a fibroblast–CD8 + T‐cell adhesion circuit, supported by loss‐of‐function evidence in mice and correlative human data, from an emerging therapy–conditioned tumor–heart extracellular vesicle axis supported mainly by breast cancer models. These pathways may converge on fibrotic stiffness, microvascular dysfunction, and electrical uncoupling; however, direct cross‐circuit interaction and drug‐independent sufficiency remain unproven. We integrate established clinical risk modifiers with this framework, specify causal criteria, and propose spatial multiomics, living myocardial slices, tumor‐bearing systems, and longitudinal phenotyping to test circuit persistence. This evidence‐calibrated model shifts the goal from cataloging cell‐intrinsic pathways to identifying mechanism‐resolved biomarkers and therapeutically targetable communication nodes while preserving antitumor efficacy.
Related
- Genetic Susceptibility to Anthracycline-Induced Cardiotoxicity in Australian Pediatric Cancer Patients
- Late Anthracycline Cardiotoxicity Mimicking Arrhythmogenic Cardiomyopathy in a Young Adult
- Exploring the protective mechanism of Huangqishengmaiyin against anthracycline-induced cardiotoxicity in breast cancer with concomitant gut microbiota modulation
- Cardiotoxicity of Immune Checkpoint Inhibitors with Anthracycline Chemotherapy in Triple-Negative Breast Cancer.
- Dynamic Changes in Apolipoproteins During Anthracycline Therapy: An Exploratory Study of Potential Biomarkers of Cardiotoxicity in Breast Cancer Patients
BibTeX
@article{wang2026anthracycline,
title = {{Anthracycline Cardiotoxicity as Multicellular Network Failure: Cardiac Niche Reprogramming and Pathological Cell–Cell Communication}},
author = {Shuhui Wang and Quanquan Ding and Siyue Ding and Chunli Liu and Qian Li},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.053190},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.053190},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Anthracycline Cardiotoxicity as Multicellular Network Failure: Cardiac Niche Reprogramming and Pathological Cell–Cell Communication
AU - Shuhui Wang
AU - Quanquan Ding
AU - Siyue Ding
AU - Chunli Liu
AU - Qian Li
PY - 2026
DA - 2026/10/23
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.053190
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.053190
AB - Anthracyclines are essential anticancer agents, yet a cardiomyocyte‐centered model incompletely explains why cardiac injury can be delayed, progressive, and poorly captured by resting ejection fraction. We frame anthracycline cardiotoxicity as a multicellular network failure within the cardiac niche: the spatially organized interactions among cardiomyocytes, fibroblasts, endothelial and immune cells, extracellular matrix, and circulating signals. Cardiomyocyte stress initiates injury, whereas pathological communication may propagate it. We distinguish a fibroblast–CD8 + T‐cell adhesion circuit, supported by loss‐of‐function evidence in mice and correlative human data, from an emerging therapy–conditioned tumor–heart extracellular vesicle axis supported mainly by breast cancer models. These pathways may converge on fibrotic stiffness, microvascular dysfunction, and electrical uncoupling; however, direct cross‐circuit interaction and drug‐independent sufficiency remain unproven. We integrate established clinical risk modifiers with this framework, specify causal criteria, and propose spatial multiomics, living myocardial slices, tumor‐bearing systems, and longitudinal phenotyping to test circuit persistence. This evidence‐calibrated model shifts the goal from cataloging cell‐intrinsic pathways to identifying mechanism‐resolved biomarkers and therapeutically targetable communication nodes while preserving antitumor efficacy.
SN - 2047-9980
ER -