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Review
. 2022 Dec 12;23(24):15769.
doi: 10.3390/ijms232415769.

When Two Maladies Meet: Disease Burden and Pathophysiology of Stroke in Cancer

Ming-Yee Sun  1   2   3 , Sonu M M Bhaskar  1   2   4   5   6
Affiliations
Review

When Two Maladies Meet: Disease Burden and Pathophysiology of Stroke in Cancer

Ming-Yee Sun et al. Int J Mol Sci. .

Abstract

Stroke and cancer are disabling diseases with an enormous global burden, disproportionately affecting vulnerable populations and low- and middle-income countries. Both these diseases share common risk factors, which warrant concerted attention toward reshaping population health approaches and the conducting of fundamental studies. In this article, an overview of epidemiological trends in the prevalence and burden of cancer and stroke, underlying biological mechanisms and clinical risk factors, and various tools available for risk prediction and prognosis are provided. Finally, future recommendations for research and existing gaps in our understanding of pathophysiology. Further research must investigate the causes that predispose patients to an increased risk of stroke and/or cancer, as well as biomarkers that can be used to predict growing morbidity and mortality.

Keywords: blood clot; cancer; chemotherapy; radiotherapy; stroke; thrombosis.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Overview of pathophysiological mechanisms of stroke in cancer patients. Abbreviations: NET: neutrophil extracellular trap; TIA: transient ischemic attack.
Figure 2
Figure 2
Cancer-induced hypercoagulability on a molecular level. Impact of cancer on the coagulation cascade. Inflammatory cytokines such as TNF-a, IL-1, and IL-6 induce endothelial cells, monocytes, and cancer cells to express tissue factor (TF), exerting a parallel action to potentiate the coagulation cascade. Protein C, which regulates Factor VIIIa and Factor Va (cofactors in the activation of Factor X and prothrombin), is inhibited by these cytokines. TF binds to Factor VII, potentiating the coagulation cascade by proteolytically activating Factor IX and Factor X, thus leading to the formation of thromboses and subsequent stroke. CP, a cysteine protease, is released in most malignancies and directly cleaves. Factor X → Xa independently of FVII, resulting in thrombin generation. Mucin is a potent procoagulant that directly activates prothrombin into thrombin, mostly secreted by adenocarcinomas. Abbreviations: CP: cancer procoagulant; TF: tissue factor; PL: phospholipids; NETs: neutrophil extracellular trap; TNF: tumor necrosis factor; IL: interleukin; and CP: cancer procoagulant.
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