Hemostasis and cancer: Impact of haemostatic biomarkers for the prediction of clinical outcomes in patients with cancer

Abstract

Patients with cancer are characterized by a dysregulation of the hemostatic system and systemic hypercoagulability. Different components of the hemostatic system are involved in tumor‐promoting mechanisms including primary tumor growth, cancer cell invasion, immune evasion, angiogenesis, and the metastatic process. Therefore, different degrees of systemic hemostatic activation in patients with cancer can reflect distinct underlying biological phenotypes of cancer and seem to correlate with cancer aggressiveness. Peripheral blood levels of hemostatic biomarkers, indicating the activation status of different parts of the hemostatic system including the coagulation cascade, fibrinolytic activity, platelet activation, or endothelial activation, can be used to reflect cancer‐associated systemic hypercoagulability. Thereby, hemostatic biomarkers represent promising candidates to investigate as surrogate markers for underlying cancer activity and progression dynamics and therefore as biomarkers for the prediction of clinical outcomes in cancer patients. In the present review, we provide an up‐to‐date summary of available data on hemostatic biomarkers for prognostication of overall survival and prediction of therapy response in patients with cancer, including specific oncologic treatment settings for potential clinical application. We provide a thorough discussion on potential clinical implementation and current limitations and highlight the most promising emerging biomarkers that might be used to contribute to risk‐stratified, personalized oncologic decision making in the future.

Discovery of 5-Hydroxy-1,4-naphthoquinone (Juglone) Derivatives as Dual Effective Agents Targeting Platelet-Cancer Interplay through Protein Disulfide Isomerase Inhibition

“…To a stirred suspension of 7 (700 mg, 4.0 mmol) in H 2 O (40 mL) was added dimethylamine (2 M in THF) (4 mL). After stirring for 2 h, the reaction mixture was concentrated under reduced pressure and purified by column chromatography (silica gel; EtOAc/hexane = 1/7) to give 23 (174 mg, 20%) and 24 (50 mg, 6%) as red solids; R f = 0.33 (23) 2,8-Dihydroxynaphthalene-1,4-dione (25). To a stirred solution of 23 (50 mg, 0.23 mmol) in 1,4-dioxane (1 mL) was added 10% HCl (aq) (255 μL).…”

“…20,22 The flavonoid glycoside isoquercetin (5, Figure 1b) has been reported to exhibit antiplatelet activity, 11 and demonstrated efficacy in preventing platelet activation and platelet-dependent thrombin generation in a phase II/III cancer clinical trial with no serious adverse events. 24 Because cancer-induced platelet activation and hypercoagulability are frequently observed in cancer patients, 25 these results reveal a potential role for PDI inhibitors in the treatment of cancer and thrombotic complications by blocking the platelet−cancer interaction. 26,27 Juglone (JUG, 7, Figure 2), 5-hydroxy-1,4-naphthoquinone, is an allelochemical found in walnut plants such as Juglans regia (J. regia).…”

“…On the other hand, several noncovalent inhibitors were developed, such as BAP-2 ( 4 ), isoquercetin ( 5 ), and ML359 ( 6 ), exhibiting the inhibition mechanism of blocking the substrate binding site in the b′ domain. , The flavonoid glycoside isoquercetin ( 5 , Figure b) has been reported to exhibit antiplatelet activity, and demonstrated efficacy in preventing platelet activation and platelet-dependent thrombin generation in a phase II/III cancer clinical trial with no serious adverse events . Because cancer-induced platelet activation and hypercoagulability are frequently observed in cancer patients, these results reveal a potential role for PDI inhibitors in the treatment of cancer and thrombotic complications by blocking the platelet–cancer interaction. , …”

Hypercoagulability State Combined with Post-Treatment Hypofibrinolysis in Invasive Breast Cancer: A Seven-Year Follow-Up Evaluating Disease-Free and Overall Survival

“…The pathomechanism of blood coagulation and fibrinolysis activation in cancer is complex and multifactorial and its exact pathophysiological pathways are still under elucidation [ 10 ]. There are multiple pathophysiological processes involved in the interplay between cancer and various components of the haemostatic system [ 11 ]. One of the key factors contributing to the development of haemostatic disorders in cancer is the tumour-cell-associated clot promotion consisting of the production of procoagulant factors by tumour cells [ 10 ].…”

Update on Thrombosis Risk in Patients with Cancer: Focus on Novel Anticancer Immunotherapies

“…[4][5][6] Further, most prominently, risk profiles for VTE and ATE largely depend on cancer-specific prothrombotic risk factors including cancer type, stage, and biology, with a known association between hypercoagulability and more aggressive clinical behavior of cancers. 2,7 Finally, the risk of cancerassociated thromboembolic events is affected by iatrogenic factors including cancer surgery, radiotherapy, and medical anticancer therapies. 5,8 Of these, certain chemotherapy agents have been linked to an increased cardiovascular risk.…”