Cardiotoxicity of Targeted Therapies in Non-Hematologic Cancers: Mechanisms, Risks and Monitoring

Abstract

Cardiotoxicity has emerged as an increasingly recognized concern in modern oncology, particularly with the growing use of targeted therapies such as small-molecule inhibitors and monoclonal antibodies. These agents have revolutionized cancer care by offering remarkable precision in selectively attacking molecular pathways essential for tumor growth and survival. However, despite their therapeutic benefits, targeted therapies may inadvertently affect the cardiovascular system, leading to adverse outcomes that can compromise both quality of life and long-term prognosis in cancer survivors. As cancer survival improves, the burden of treatment-related cardiovascular complications has become more evident, highlighting the need for early recognition, prevention, and management strategies. The mechanisms underlying cardiotoxicity from targeted therapies are highly complex and multifactorial. Unlike traditional chemotherapeutic agents, which often exert direct toxic effects on cardiomyocytes, targeted therapies may interfere with signaling pathways critical to both malignant and normal cardiovascular cellular functions. This disruption can manifest through a wide spectrum of adverse cardiovascular events, ranging from left ventricular dysfunction and arrhythmias to hypertension, thromboembolic events, and accelerated atherosclerosis. Importantly, these toxicities are often unpredictable and may vary according to the drug class, dosage, treatment duration, and patient profile. Risk factors for cardiotoxicity extend beyond the pharmacological properties of targeted therapies. Patient-specific characteristics—such as preexisting cardiovascular disease, age, sex, genetic predisposition, and concurrent exposure to other cardiotoxic agents—significantly modulate individual susceptibility. Moreover, the coexistence of traditional cardiovascular risk factors, including hypertension, diabetes, and dyslipidemia, may further exacerbate the incidence and severity of treatment-related complications. Identifying and stratifying patients according to these risk factors is therefore a crucial step in optimizing care. Given the rising incidence and clinical impact of treatment-related cardiotoxicity, effective management necessitates a multidisciplinary and integrated approach. Collaboration between oncologists, cardiologists, and emerging cardio-oncology units is essential to ensure timely detection and intervention. Regular cardiac monitoring, individualized risk assessment, and the prompt recognition of early warning signs form the cornerstone of preventive care. Furthermore, evidence-based strategies for mitigating cardiovascular risk ranging from lifestyle modification and optimization of comorbidities to pharmacological cardioprotection are increasingly being incorporated into clinical practice. In this review, we provide a focused overview of cardiotoxicity associated with targeted therapies, with particular emphasis on its underlying mechanisms, risk factors, and approaches to clinical management. By bridging oncology and cardiology perspectives, this work underscores the importance of proactive cardio-oncology collaboration to improve patient outcomes in the era of precision cancer medicine.