Mechanisms of anticancer treatment-induced arterial and venous thrombosis

Recent advances in cancer treatment have improved outcomes for patients across a wide variety of cancers. However, despite the introduction of more targeted therapies, including those that harness the body's natural immune system, cancer-associated thrombosis, particularly during therapy, is a significant clinical problem associated with poorer outcomes. Although venous thromboembolism is more common, arterial events cause significant morbidity and are frequently fatal. In addition to the well-established chemotherapeutic regimens, multiple therapies are now used in the first-line setting, including antibody-based treatments, immunotherapy, and hormone receptor modulators. Many cancers are now being managed as chronic diseases with long-term maintenance therapies in an increasingly older patient population with significant comorbidities. With this change in the treatment landscape, predictive biomarkers are needed to effectively identify patients and treatments associated with the highest risk of thrombosis in the current cancer population. Although cancer-associated thrombosis has been extensively studied, the specific mechanisms by which cancer therapy causes thrombosis remain poorly understood. The pathogenesis of immunothrombosis associated with cancer treatments in particular is poorly defined. Focusing on solid tumors, the aim of this narrative review is to explore our current understanding of the pathogenesis of thrombotic effects of systemic cancer treatment. These include coagulation activation, vascular endothelial damage, procoagulant effects of material from dead and dying tumor cells, as well as the role of inflammatory mediators. Greater understanding of pathogenesis of treatment-related cancer-associated thrombosis will lead to the identification of more effective biomarkers to guide thromboprophylaxis.