Cancer treatment-related cardiotoxicity, molecular mechanism, challenges, and research trends

Abstract

Cancer treatment-related cardiotoxicity (CTRC) encompasses a spectrum of cardiovascular complications associated with chemotherapy, targeted therapy, and radiotherapy. This review synthesizes recent mechanistic insights to delineate distinct pathological pathways: anthracyclines provoke oxidative mitochondrial damage and disrupt cardiomyocyte iron homeostasis; HER2-targeted therapies inhibit the PI3K-Akt survival pathway, compromising contractile function and calcium regulation; tyrosine kinase inhibitors impair VEGF and PDGF signaling, inducing endothelial dysfunction and microvascular rarefaction; immune checkpoint inhibitors activate T-cell-mediated myocarditis; and thoracic radiation initiates endothelial inflammation followed by TGF-β–dependent fibrotic remodeling. These mechanism-specific injuries follow a characteristic clinical sequence, with arrhythmias and myocarditis emerging acutely, subclinical contractile dysfunction developing within months, and overt heart failure or vascular stenosis manifesting years post-treatment. We highlight the critical roles of advanced imaging and biomarker-based surveillance in early detection, and underscore evidence-based cardioprotective interventions that maintain anticancer efficacy while mitigating cardiovascular risk.

Introduction

Recent advances in cancer therapeutics, driven by the development of chemotherapy and targeted agents, have markedly improved treatment outcomes and patient survival [1, 2]. These potent antitumor modalities, however, are accompanied by a growing clinical challenge: treatment-related cardiotoxicity [3]. Ranging from reversible cardiac dysfunction to irreversible cardiomyopathies, cardiotoxicity has emerged as a critical concern at the interface of oncology and cardiology [4, 5].

Cancer treatment-related cardiotoxicity (CTRC) encompasses a spectrum of complex and incompletely elucidated mechanisms [6], which has hindered the development of precise or personalized therapeutic approaches [3, 5, 7]. The primary manifestations of CTRC are categorized as chemotherapy-induced, targeted therapy-associated, and radiotherapy-related [8]. Each category involves distinct molecular pathways, including oxidative stress, critical signaling pathway disruption, and provoked immune responses, which collectively impair the cardiovascular system, and several excellent reviews have summarized the general mechanisms of CTRC [9, 10].

To ensure a current and systematic review, we conducted a literature search across PubMed, Web of Science, and Google Scholar, focusing on publications from the past five years and placing special emphasis on recent advancements reported between 2023 and 2024. The present review provides a distinct contribution in several key aspects. First, we integrate radiation-induced heart toxicity into a unified molecular ontology alongside chemotherapy- and targeted therapy-induced injury, thereby establishing a cross-modality framework for understanding cardiotoxic pathways. Second, we systematically map each pathway to a defined clinical timeline—from hyper-acute to chronic phases—and link them to currently available protective interventions, translating mechanistic insights into stage-specific clinical recommendations. Third, we incorporate recent evidence from pre-clinical studies and clinical trials published between 2023 and 2025 not covered in previous reviews. Collectively, these features offer clinicians and researchers an updated, mechanism-based, and clinically actionable roadmap that complements—rather than overlaps with—existing publications. By integrating scientific evidence, clinical expertise, and emerging perspectives, our goal is to equip medical professionals with the knowledge to optimize oncologic efficacy while preserving cardiac function, ultimately improving treatment safety and patient outcomes.

CTRC

The integration of cancer treatment and cardiovascular health has become a clinically significant concern in oncology [11]. CTRC encompasses a spectrum of adverse cardiovascular effects caused by various anticancer modalities, ranging from conventional chemotherapy to newer targeted therapies and immunotherapies [3]. Although these treatments are often essential for survival, they may inadvertently induce cardiac injury, resulting in diverse cardiovascular manifestations [12].

As summarized in Table 1, CTRC presents with a broad spectrum of cardiovascular abnormalities, which can be classified into acute and chronic forms [13]. Acute manifestations—such as arrhythmias, myocarditis, and pericarditis—typically occur shortly after treatment initiation [14]. In contrast, chronic manifestations, including heart failure, cardiomyopathy, and vascular dysfunction, often emerge months to years after therapy completion [15]. The development and severity of CTRC are influenced by multiple factors, including treatment type, cumulative dose, patient age, pre-existing cardiovascular conditions, and genetic susceptibility [16].

Table 1.

Clinical features and monitoring of major cancer Treatment-Related cardiotoxicities

Therapy Class	Example Agents	Key Mechanisms	Clinical Manifestations	Incidence	Reversibility	Monitoring Biomarkers	References
Chemotherapy (Anthracyclines)	Doxorubicin, Epirubicin	Topo-IIβ inhibition, ROS, Oxidative stress, Ferroptosis, Mitochondrial dysfunction	Dilated cardiomyopathy, HFrEF	5–10%	Largely irreversible	Troponin, BNP/NT-proBNP	[35, 36]
Targeted Therapy (Anti-HER2)	Trastuzumab, Pertuzumab	HER2 signaling blockade, Impaired survival/repair	Asymptomatic LVEF decline, HF	3–15%	Often reversible	LVEF, Troponin	[45]
Targeted Therapy (TKIs)	Sunitinib, Imatinib	VEGFR/PDGFR inhibition, Endothelial dysfunction, hERG channel blockade	Hypertension, HFpEF, QT prolongation, Arrhythmias	5–20%	Variable	BP monitoring, ECG, LVEF	[55, 59]
Immunotherapy (ICIs)	Pembrolizumab, Nivolumab	T-cell activation against cardiac antigens, NLRP3 inflammasome activation, Myocarditis	Myocarditis, Arrhythmias, Cardiogenic shock	~ 1–2%	Variable (requires immunosuppression)	Troponin, CRP, ECG	[65, 66]
Radiotherapy	-	Endothelial damage, Chronic inflammation, Oxidative stress, Fibrosis (TGF-β)	Coronary artery disease, Valvular disease, Restrictive cardiomyopathy	Increases over time	Irreversible, progressive	Stress testing, Coronary calcium scoring, Echo	[79]

ROS reactive oxygen species; VEGFR vascular endothelial growth factor receptor; PDGFR platelet-derived growth factor receptor; LVEF left ventricular ejection fraction; HF Heart failure; HFpEF heart failure with reduced ejection fraction; HFpEF Heart failure with preserved ejection fraction; CRP C-reactive protein; ECG electrocardiogram; BNP brain natriuretic peptide

The prevalence of CTRC varies substantially across cancer types and treatment regimens [3]. This clinical landscape continues to evolve with the expanding use of targeted therapies and immunotherapies, which have introduced novel cardiotoxic profiles [17]. While anthracyclines and human epidermal growth factor receptor 2 (HER2)-targeted agents remain well-established causes of chemotherapy-induced cardiac injury [18], newer drug classes—including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs)—have further broadened the spectrum of cardiovascular complications [19, 20]. Reported incidence rates range from less than 1% to over 20%, reflecting differences in therapeutic protocols and patient characteristics [21, 22]. This substantial variability highlights the critical need for vigilant monitoring and tailored management of CTRC to balance oncologic efficacy with cardiovascular safety.

Progress in elucidating the mechanisms of CTRC has accelerated the development of strategies for its prevention, early detection, and treatment [13]. Cardioprotective agents, including angiotensin-converting enzyme inhibitors (ACEIs) [23, 24] and beta-blockers [25, 26], are under investigation as potential interventions to mitigate cardiac injury during anticancer therapy. Furthermore, the emerging discipline of cardio-oncology—illustrated in Fig. 1—seeks to integrate oncologic and cardiovascular care, enabling a holistic approach to patients at risk of CTRC [13, 27]. Promising tools for risk stratification and treatment guidance include circulating biomarkers [28, 29], advanced imaging techniques [30], and genetic profiling [31] Despite these advances, CTRC management remains complex and necessitates close multidisciplinary collaboration among oncologists, cardiologists, and allied health professionals [3]. In the following sections, we examine the molecular mechanisms and clinical implications of chemotherapy-induced and targeted therapy-associated cardiotoxicity.

Fig. 1.

Cardio-oncology: (A) key components; (B) developmental timeline

Chemotherapy-Induced cardiotoxicity

Anthracyclines

Chemotherapeutic agents constitute a cornerstone in the management of diverse malignancies [32]. Among them, anthracyclines—such as doxorubicin, epirubicin, and daunorubicin—are widely employed due to their potent efficacy in inhibiting cancer cell proliferation [33, 34]. However, their clinical utility is substantially limited by a well-recognized risk of dose-dependent cardiotoxicity [35]. The pathogenesis of anthracycline-induced cardiac injury involves a multifaceted cascade, primarily initiated by reactive oxygen species (ROS) overproduction and consequent oxidative stress in myocardial tissue [36]. Upon administration, anthracyclines undergo redox cycling, a process characterized by continuous transitions between reduced and oxidized states [37, 38]. This cyclic electron transfer promotes the excessive generation of ROS, including superoxide anions, hydrogen peroxide, and hydroxyl radicals [38]. The resulting redox imbalance overwhelms endogenous antioxidant systems in cardiomyocytes, leading to widespread oxidative damage to cellular structures [39].

The oxidative stress induced by anthracyclines triggers a cascade of detrimental cellular events [40]. A key consequence is lipid peroxidation, which disrupts the integrity of cellular membranes [41]. Concurrently, protein oxidation impairs structural and functional integrity [42], while oxidative DNA damage induces mutagenic alterations and compromises cellular replication fidelity [43]. Collectively, these insults contribute to the development of cardiomyopathy, characterized by progressive weakening of the myocardium and impaired contractile function [27]. Furthermore, anthracyclines disrupt iron homeostasis in cardiomyocytes, which amplifies oxidative injury and establishes a self-perpetuating cycle of cardiotoxicity [44, 45]. Beyond these established mechanisms, recent evidence underscores the role of ferroptosis—an iron-dependent, lipid peroxidation-driven form of regulated cell death—as a critical pathway in anthracycline-induced cardiomyocyte loss.

HER2 targeted therapies

HER2-targeted therapies, particularly trastuzumab, have revolutionized the treatment of HER2-positive breast cancer [46]. However, their clinical application is complicated by a recognized risk of cardiotoxicity [18]. The HER2 receptor is expressed not only in cancer cells but also in cardiomyocytes, where it plays a critical role in maintaining cardiac function [47, 48]. The HER2 signaling pathway is essential for cardiomyocyte survival, contractility, and calcium homeostasis [49]. Trastuzumab, as a monoclonal antibody targeting HER2, binds to these receptors in both malignant and cardiac cells [50]. While its antitumor effect is achieved by inhibiting HER2-driven proliferation in cancer cells [51], this same mechanism disrupts vital signaling in cardiomyocytes.

Nevertheless, the cardiac implications of HER2 inhibition demand careful attention. In cardiomyocytes, the HER2 signaling pathway plays a fundamental role in regulating contractile function, calcium homeostasis, and cell survival [48]. Inhibition of this pathway disrupts these critical processes, leading to a progressive decline in cardiac performance. Key consequences include impaired contractility, dysregulated calcium handling, and enhanced susceptibility to apoptosis [52]. These pathological changes collectively contribute to the development of heart failure over time. At the molecular level, trastuzumab-mediated HER2 blockade suppresses the PI3K/AKT signaling cascade, a crucial survival pathway in cardiomyocytes. This suppression is characterized by reduced AKT phosphorylation and subsequent activation of apoptotic mechanisms, as demonstrated in studies of trastuzumab-induced cardiotoxicity [2].

Targeted therapy-related cardiotoxicity

Tyrosine kinase inhibitors (TKIs)

TKIs represent a transformative class of anticancer agents that selectively target molecular pathways essential for tumor growth and progression [53]. Despite their well-established efficacy, TKIs—including sunitinib, imatinib, and dasatinib—are associated with significant cardiotoxicities that necessitate careful cardiovascular monitoring and management [54].

A central mechanism underlying TKI-induced cardiotoxicity involves inhibition of the vascular endothelial growth factor (VEGF) signaling pathway [55]. VEGF serves as a critical regulator of vascular integrity, maintaining endothelial cell function and supporting vascular stability [56]. TKI-mediated disruption of VEGF signaling impairs angiogenesis and compromises microvascular perfusion [57, 58]. In the heart, this leads to reduced myocardial capillary density, endothelial dysfunction, and microvascular rarefaction, establishing a pathological foundation for subsequent cardiac complications [59].

The cardiovascular toxicity of TKIs involves multifaceted mechanisms beyond VEGF pathway inhibition. A principal mechanism involves disruption of key signaling pathways vital for cardiac function and structural maintenance [60]. Specifically, inhibition of platelet-derived growth factor (PDGF) and c-kit signaling—pathways crucial for maintaining cardiac cellular homeostasis and regulating structural adaptation—compromises both myocardial contractility and structural integrity [54, 61]. This dual disruption contributes significantly to the progression of TKI-induced cardiac dysfunction.

Beyond these structural and functional impacts, TKIs demonstrate considerable electrophysiological toxicity. Certain agents, notably imatinib, directly interfere with the human ether-à-go-go-related gene (hERG) potassium channel, which governs the repolarization phase of the cardiac action potential [62, 63]. This interaction delays myocardial repolarization, resulting in measurable prolongation of the QT interval on surface electrocardiogram (ECG). Such QT interval prolongation establishes a susceptible substrate for the development of serious ventricular arrhythmias, most notably torsades de pointes [64].

ICIs

ICIs, a class of immunotherapeutic agents including pembrolizumab, nivolumab, and ipilimumab, have transformed the landscape of cancer treatment [19]. While these agents enhance T cell-mediated antitumor immunity, their mechanism of action can precipitate loss of self-tolerance, leading to a spectrum of immune-related adverse events [65]. Among the most serious of these complications is myocarditis, an inflammatory condition of the myocardium that represents a potentially life-threatening form of ICI-associated cardiotoxicity [66].

The pathogenesis of ICI-associated myocarditis is driven by the aberrant activation of the immune system. Central to this process is the activation and clonal expansion of T cells, along with the recruitment and polarization of macrophages, which collectively initiate a damaging inflammatory cascade within the myocardium [67, 68]. These activated immune cells infiltrate cardiac tissue, where they may mistakenly recognize self-antigens present on cardiomyocytes, leading to a targeted immune attack [69]. A critical upstream event amplifying this response is the activation of the NLRP3 inflammasome within immune cells, resulting in the maturation and secretion of potent pro-inflammatory cytokines such as IL-1β and IL-18. This local inflammatory response is further intensified by a systemic release of cytokines, including interleukins and tumor necrosis factor (TNF), which collectively establish a pronounced pro-inflammatory milieu in the cardiac microenvironment [70]. This cycle of immune activation and inflammation progressively damages cardiomyocyte structure and compromises cardiac function.

The sustained immune attack ultimately induces cardiomyocyte death through apoptosis and necrosis. This loss of functional myocardium triggers a reparative response dominated by cardiac fibrosis, characterized by the excessive deposition of extracellular matrix proteins that form scar tissue [71]. As fibrotic tissue progressively replaces healthy myocardium, it disrupts the electrical conduction system and impairs ventricular compliance. This structural remodeling leads to a progressive decline in cardiac output and pumping efficiency. The culmination of this pathological trajectory is the development of heart failure, a clinical syndrome marked by the heart’s inability to maintain adequate circulatory support for bodily needs [72]. Thus, the same immunologic mechanisms that confer antitumor efficacy with ICIs can also initiate a destructive process leading to irreversible cardiac dysfunction.

Other targeted therapies and cardiotoxicity

Beyond ICIs and TKIs, cardiac toxicity has been documented with other targeted therapeutic classes [27]. Clinically relevant examples include proteasome inhibitors such as bortezomib for multiple myeloma and epidermal growth factor receptor (EGFR) inhibitors like lapatinib for breast cancer, both of which have demonstrated potential cardiotoxic effects [73, 74].

The cardiotoxic mechanisms associated with these targeted therapies, while diverse, share several common pathophysiological features. Central among these are oxidative stress, disruption of key cardiac signaling pathways, and mitochondrial dysfunction, which collectively contribute to myocardial injury [75]. Mitochondrial impairment represents a particularly critical mechanism in targeted therapy-induced cardiotoxicity [12]. As essential regulators of cellular energy metabolism and redox balance, mitochondria sustain cardiomyocyte function through continuous adenosine triphosphate (ATP) production. Targeted therapeutic agents can disrupt mitochondrial integrity and function, leading to reduced ATP generation and increased ROS production [76]. The resulting mitochondrial impairment leads to a critical energy deficit in cardiomyocytes, directly compromising their contractile function and the heart’s pumping efficiency. This bioenergetic failure manifests as weakened cardiac contraction and impaired relaxation with each heartbeat. As mitochondrial dysfunction progresses, the diminished production of cellular energy sources undermines cardiomyocyte viability and contractile performance. Collectively, oxidative stress, disrupted signaling pathways, and mitochondrial dysfunction represent interconnected mechanisms that drive targeted therapy-induced cardiotoxicity. Among these, mitochondrial dysfunction serves as a central pathway, highlighting the crucial balance required for maintaining cardiac function during anticancer treatment.

Radiotherapy related cardiotoxicity

Radiotherapy represents another significant source of CTRC alongside systemic treatments [3, 77]. While essential for managing various malignancies, radiation exposure to cardiac structures—particularly when the heart lies within the treatment field—can lead to substantial cardiovascular complications [77]. Radiation-induced heart toxicity (RIHT) originates from the damaging effects of ionizing radiation on myocardial tissue and the vascular system [78].

RIHT develops through a sequence of interconnected acute and chronic pathological processes that collectively determine long-term cardiovascular outcomes [79]. The initial injury phase is characterized by direct endothelial damage, which initiates a cascade of inflammatory activation and oxidative stress within the cardiac microenvironment [80]. These acute cellular responses establish the foundation for progressive tissue remodeling, manifested clinically as accelerated coronary atherosclerosis and diffuse myocardial fibrosis [71]. Central to this fibrotic transformation is the sustained activation of transforming growth factor-beta (TGF-β) signaling pathways, which orchestrates extensive extracellular matrix deposition and architectural reorganization of myocardial tissue [81]. This structural remodeling progressively impairs cardiac function, as expanding fibrotic tissue disrupts electrical conduction and compromises ventricular compliance. The functional deterioration ultimately manifests as clinically significant cardiac impairment, substantially increasing the risk of major cardiovascular events. Among the most serious consequences are myocardial infarction and heart failure, which represent the culmination of the pathological continuum initiated by radiation exposure [78]. Thus, the pathogenesis of RIHT follows a temporal progression from acute cellular damage to chronic cardiovascular dysfunction. This multifaceted process, integrating endothelial injury, sustained inflammation, oxidative stress, and the coordinated development of atherosclerosis and fibrosis, underscores the complex pathophysiology of radiation-induced cardiotoxicity.

Research on cardioprotective strategies against RIHT continues to advance. Current investigations focus on antioxidant agents such as vitamin E and N-acetylcysteine, which may counteract radiation-induced oxidative stress [82, 83]. Additionally, established cardioprotective medications including angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers demonstrate potential in preventing or mitigating RIHT-related cardiac injury [84, 85]. The development of personalized treatment protocols that optimize radiotherapy efficacy while minimizing cardiac risk remains essential. This approach necessitates strengthened collaboration between oncologists and cardiologists through integrated clinical decision-making [3, 85].

Future trends and research prospects

The evolving landscape of cancer therapy demands equally advanced strategies to manage cardiotoxicity. Future research will likely focus on several key areas to achieve this goal:

Precision oncology and individualized approaches: The integration of precision medicine into cardio-oncology represents a paradigm shift. Genomic profiling—encompassing both tumor and germline DNA—is identifying critical genetic determinants of cardiotoxicity risk, such as variants in TTN and RARG [86–88]. This genetic insight enables moving beyond one-size-fits-all approaches toward risk-adapted therapy and personalized cardioprotection strategies.

Emerging technologies are further refining this precision framework. Next-generation sequencing panels and single-cell RNA sequencing allow for tracking of expanded T-cell clones (e.g., CD8⁺ CXCR3⁺) in immunotherapy-related myocarditis [89]. Concurrently, exosomes are being investigated as both dynamic biomarkers of cardiac injury and potential vehicles for targeted drug delivery [90]. Artificial intelligence applied to cardiac strain imaging, along with the development of patient-specific digital twins, creates unprecedented opportunities for virtual dose optimization and preemptive risk management [91]. These integrated approaches facilitate a transition from population-based guidelines to truly individualized patient care in cardio-oncology.

Novel cardioprotective agents: Research into novel cardioprotective strategies is advancing along several promising fronts [75]. Mitochondria-targeted therapeutics, such as mitoquinone, demonstrate significant potential in attenuating oxidative stress within cardiomyocytes [92]. Concurrently, nanotechnology platforms are being engineered for the targeted delivery of cardioprotective agents to cardiac tissues, enhancing local efficacy while minimizing systemic exposure [93, 94]. The exploration of biomimetic compounds derived from natural products further expands the repertoire of potential cardioprotectants [95]. Integration of these complementary approaches is expected to yield tailored cardioprotection regimens aligned with specific cancer therapies.

Nanomedicine offers a distinct strategy for mitigating chemotherapy-associated cardiotoxicity through improved drug targeting. Nanoparticle encapsulation of chemotherapeutic agents, exemplified by liposomal doxorubicin (e.g. Doxil), enhances tumor-specific delivery while reducing systemic distribution. This approach has demonstrated substantially lower cardiotoxicity compared to conventional formulations, with some studies reporting a relative risk as low as 0.35. Further refinement through surface functionalization with targeting ligands enhances tumor selectivity and minimizes off-target effects. Emerging “smart” nanocarriers designed to respond to specific tumor microenvironmental cues represent the next frontier in balancing anticancer efficacy with cardiovascular safety, potentially expanding the therapeutic window for otherwise dose-limited chemotherapies.

Integration of artificial intelligence and big data: The convergence of artificial intelligence (AI) and big data analytics holds transformative potential for optimizing cancer treatment while mitigating associated cardiotoxicity [91, 96]. Machine learning algorithms can now integrate diverse patient parameters—including treatment regimens, genomic profiles, and clinical history—to generate individualized predictions of cardiovascular risk [97]. Furthermore, wearable devices and remote monitoring technologies enable continuous assessment of cardiac function. When coupled with AI-driven analytical platforms, these data streams provide real-time insights into treatment response and early signs of cardiac compromise [98]. This integrated approach facilitates dynamic, evidence-based adjustments to therapeutic strategies, empowering clinicians to balance oncologic efficacy with cardiovascular safety throughout the course of treatment.

Imaging advancements for early detection: Technological progress in cardiac imaging is significantly improving the early identification of treatment-related cardiotoxicity [99]. Advanced echocardiographic methods—particularly myocardial strain imaging and three-dimensional echocardiography—provide sensitive assessment of myocardial mechanics and functional changes [100, 101]. Concurrently, cardiac magnetic resonance imaging with quantitative mapping techniques (e.g., T1, T2) enables detailed characterization of myocardial tissue composition, detecting subclinical alterations prior to symptomatic manifestation [30, 102, 103]. The incorporation of artificial intelligence into image interpretation further augments detection capability, identifying subtle patterns of cardiac injury that may elude conventional analysis [104]. Collectively, these developments are establishing a foundation for preemptive intervention in cardiotoxicity management.

Refinement of Cardio-Oncology clinical guidelines: The growing recognition of cancer therapy-related cardiovascular toxicities has accelerated the development of dedicated cardio-oncology guidelines [3]. Through multidisciplinary collaboration among oncologists, cardiologists, and translational researchers, comprehensive clinical frameworks have been established that address the full spectrum of patient management—from pre-treatment risk stratification through longitudinal monitoring and targeted intervention [85]. These evidence-based protocols provide structured approaches for mitigating cardiovascular complications while maintaining optimal oncologic treatment intensity. As novel therapeutics and monitoring technologies continue to emerge, these guidelines will undergo iterative refinement, ensuring that clinical practice remains aligned with the evolving evidence base to maximize both cancer outcomes and cardiovascular health.

Long-Term survivorship care in Cardio-Oncology: The expanding cohort of long-term cancer survivors has underscored the necessity of developing comprehensive survivorship care models that extend beyond oncologic surveillance to include systematic cardiovascular follow-up [105]. Specialized cardiac rehabilitation programs are increasingly being implemented for this population, integrating supervised exercise training, nutritional counseling, and structured cardiovascular risk factor monitoring to ameliorate treatment-related cardiovascular sequelae [3, 106]. Concurrently, growing evidence elucidates the persistent inflammatory pathways linking cancer biology to progressive cardiovascular damage, informing the development of targeted strategies for preventing late-onset cardiac complications in survivors [107, 108]. The continued refinement of these multidimensional survivorship frameworks will be essential for preserving cardiovascular health and maintaining quality of life throughout the survivorship continuum.

The evolving landscape of cardio-oncology is being shaped by transformative advances in precision medicine, innovative technologies, and multidisciplinary integration. These developments are redefining the therapeutic paradigm by enabling more precise risk stratification, earlier detection of cardiotoxicity, and implementation of targeted cardioprotective strategies. Through continued collaboration between oncology and cardiovascular medicine, the field is moving toward a future where effective cancer treatment no longer comes at the expense of cardiovascular health, ultimately improving overall survivorship outcomes and quality of life for cancer patients.

Conclusion

In summary, CTRC represents a multifaceted challenge in modern oncology practice. The present review provides distinct contributions by: (1) incorporating radiotherapy-induced cardiotoxicity into a unified framework; (2) harmonizing interdisciplinary terminology; and (3) systematically linking molecular mechanisms to corresponding early-detection techniques (e.g., strain imaging, cardiac MRI T1-mapping) and evidence-based cardioprotective strategies.

As illustrated in Fig. 2, diverse anticancer modalities—including chemotherapy, targeted agents, immunotherapy, and radiotherapy—can induce cardiac injury through interconnected pathways involving oxidative stress, disruption of survival signaling, immune activation, and fibrotic remodeling. These insults manifest clinically as electrolyte disturbances, myocardial ischemia, direct cardiomyocyte damage, and radiation-associated heart disease. While contemporary cancer therapies have significantly improved oncologic outcomes, they necessitate heightened vigilance regarding cardiovascular sequelae. Implementing structured surveillance protocols—incorporating advanced imaging modalities such as strain echocardiography and biomarker-guided monitoring—enables early detection of subclinical dysfunction. Subsequent initiation of guideline-directed cardioprotective therapies can then mitigate progression to overt cardiovascular disease. Moving forward, refining risk stratification through novel biomarkers, validating multidisciplinary management models, and developing mechanism-specific protective strategies will be crucial for optimizing long-term outcomes for cancer patients and survivors.

Fig. 2.

Molecular mechanisms of anticancer drug-induced cardiotoxicity

Author contributions

This study was conceived by PL, YLL, and JYL. PL, WQY and LMW were responsible for creating the figures and tables, while WQY, JYL, and LMW contributed to drafting the manuscript. The final version of the manuscript was revised by PL, YLL, KML and YMZ. All authors have reviewed and approved the final manuscript.

Funding

This work was supported by National Science Foundation for Scientists of China (grant number: 82460080), Doctoral Research Initiation Project of The First Affiliated Hospital of Gannan Medical University (QD202419), "Technology + Healthcare" Joint Program - Talent Project of Ganzhou (2025YLCE0100).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.