Antithrombotic Agents and Cancer

Abstract

Platelet activation is the first response to tissue damage and, if unrestrained, may promote chronic inflammation-related cancer, mainly through the release of soluble factors and vesicles that are rich in genetic materials and proteins. Platelets also sustain cancer cell invasion and metastasis formation by fostering the development of the epithelial-mesenchymal transition phenotype, cancer cell survival in the bloodstream and arrest/extravasation at the endothelium. Furthermore, platelets contribute to tumor escape from immune elimination. These findings provide the rationale for the use of antithrombotic agents in the prevention of cancer development and the reduction of metastatic spread and mortality. Among them, low-dose aspirin has been extensively evaluated in both preclinical and clinical studies. The lines of evidence have been considered appropriate to recommend the use of low-dose aspirin for primary prevention of cardiovascular disease and colorectal cancer by the USA. Preventive Services Task Force. However, two questions are still open: (i) the efficacy of aspirin as an anticancer agent shared by other antiplatelet agents, such as clopidogrel; (ii) the beneficial effect of aspirin improved at higher doses or by the co-administration of clopidogrel. This review discusses the latest updates regarding the mechanisms by which platelets promote cancer and the efficacy of antiplatelet agents.

Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes

“…Indeed, out of our compounds, derivative 9 in particular was the most potent copper reductant in this study. (2) In addition to their metal-chelating effects, this series of xanthones possessed antiplatelet effects [28], and, according to novel investigations, activated platelets increase cancer cell survival and contribute to metastasis [35,36]. Indeed, our group has recently demonstrated the solid potential of these compounds to destroy cancer cells in a variety of tumor cell lines.…”

Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies

“…Over the past two decades, there has been mounting evidence, from both basic science and clinical research, supporting a chemoprotective effect of aspirin against colorectal cancer (CRC) [1,2,3,4,5,6,7]. In 2016, this large body of evidence led the U.S. Preventive Services Task Force (USPSTF) to recommend regular use of low-dose aspirin to prevent CRC in some subgroups of patients for whom the benefits are deemed to outweigh the risks (patients aged 50 to 69 years who have a low risk of bleeding).…”

“…The mechanism of action by which aspirin exerts its anticancer effect is not fully understood, but it has been proposed that it is mediated by its antiplatelet properties and extensively reviewed elsewhere [2,3,5,6,7].…”

The History of Armand Trousseau and Cancer-Associated Thrombosis

“…Al-Samkary and Connors provide a comprehensive review on the use of direct oral anticoagulants in the treatment of VTE, with particular emphasis on efficacy and safety in cancer patients [19]. Bruno et al discuss the mechanism by which platelets can promote cancer, with a particular focus on metastasis [20]. They note that the active role played by platelets in cancer provides the rationale for the potential use of antithrombotic agents for both the prevention of cancer and the lowering of metastatic spread and consequent mortality.…”