Cancer therapies can lead to a broad spectrum of cardiovascular complications. Among these, cardiotoxicities remain of prime concern, but vascular toxicities have emerged as the second most common group. The range of cancer therapies with a vascular toxicity profile and the clinical spectrum of vascular toxic effects are quite broad. Historically, venous thromboembolism has received the greatest attention but, over the past decade, the arterial toxic effects, which can present as acute vasospasm, acute thrombosis and accelerated atherosclerosis, of cancer therapies have gained greater recognition. This Review focuses on these types of cancer therapy-related arterial toxicity, including their mechanisms, and provides an update on venous thromboembolism and pulmonary hypertension associated with cancer therapies. Recommendations for the screening, treatment and prevention of vascular toxic effects of cancer therapies are outlined in the context of available evidence and society guidelines and consensus statements. The shift towards greater awareness of the vascular toxic effects of cancer therapies has further unveiled the urgent needs in this area in terms of defining best clinical practices. Well-designed and well-conducted clinical studies and registries are needed to more precisely define the incidence rates, risk factors, primary and secondary modes of prevention, and best treatment modalities for vascular toxicities related to cancer therapies. These efforts should be complemented by preclinical studies to outline the pathophysiological concepts that can be translated into the clinic and to identify drugs with vascular toxicity potential even before their widespread clinical use.
Vascular toxic effects of cancer therapies include arterial and venous events and affect the systemic and pulmonary circulations.
Cancer therapy-related arterial toxicities can present as acute vasospasm, acute thrombosis and accelerated atherosclerosis.
The management of cancer therapy-related vascular toxicities is directed towards the underlying pathological mechanism; therefore, defining the underlying mechanism is a central element.
The best modes of pre-therapy screening, surveillance and prevention are yet to be defined.
Clinical studies and registries are needed to define more precisely the risk, risk factors and risk management of the vascular toxic effects of cancer therapies.
Experimental studies should provide insight into the pathophysiological mechanisms of cardiovascular toxic effects of cancer therapies, which might also lead to an improved understanding of cardiovascular diseases in general.
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The author received and receives support from the NIH (HL116952 and CA233610) and the Miami Heart Research Institute/Florida Heart Research Foundation.
The author declares no competing interests.
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- Systemic inflammatory response syndrome
A widespread inflammatory response that might or might not be associated with infection, characterized by an abnormal temperature (>38 °C or <36 °C) and/or leukocyte count (white blood cells >1,200 per mm3, <4,000 per mm3 or bandaemia ≥10%) and either tachycardia (heart rate >90 bpm) or tachypnoea (respiratory rate >20 breaths per min).
- Chimeric antigen receptor T cell therapy
(CAR T cell therapy). Strategy in which T cells harvested from a patient are genetically modified to recognize a specific tumour antigen in an antibody-like fashion, followed by activation of the engineered T cells before administration to the patient. Second-generation and third-generation CAR T cells have improved co-stimulatory domains, and fourth-generation CAR T cells (also known as armoured CAR T cells) express factors that enhance T cell expansion, persistence and anti-humoural activity.
- Bispecific T cell engager therapy
(BiTE therapy). Antibody constructs designed to create an immunological synapse between an effector T cell and a tumour cell by simultaneously binding to the T cell-activation molecule CD3 and a tumour-associated antigen, which is CD19 on B cells in the case of blinatumomab (approved for the treatment of B cell acute lymphoblastic leukaemia).
- Immune checkpoint inhibitor therapy
(ICI therapy). Therapy that targets internal T cell inhibitory signals known as immune checkpoints, which control T cell activity in a balance with co-stimulatory signals upon T cell receptor activation following antigen presentation and recognition. Tumours can express ligands for immune checkpoint pathways, such as programmed cell death 1, thereby mediating resistance to T cell-mediated destruction. ICIs can reverse this T cell tolerance towards tumour cells and promote T cell antitumour activity.
- Virchow’s triad
Concept named after the German pathologist Rudolf Virchow, who, in 1856, described three factors that are critically important in the development of venous thrombosis: stasis, hypercoagulability and endothelial or vascular injury.
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