Aspirin and antiplatelet treatments in cancer

Tao, Derrick; Yunga, Samuel Tassi; Williams, Craig D.; McCarty, Owen J. T.

doi:10.1182/blood.2019003977

Cited by 64 publications

(49 citation statements)

References 140 publications

(98 reference statements)

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“…This study also reported that the use of antiplatelet therapy tended to delay the deterioration of liver function in these patients (269). Recent summaries of outcomes data in cancer prevention have also highlighted the cancer mitigating role of aspirin and other agents (270).…”

Section: Platelet Activation and Aggregationmentioning

confidence: 60%

The Provocative Roles of Platelets in Liver Disease and Cancer

et al. 2021

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Both platelets and the liver play important roles in the processes of coagulation and innate immunity. Platelet responses at the site of an injury are rapid; their immediate activation and structural changes minimize the loss of blood. The majority of coagulation proteins are produced by the liver—a multifunctional organ that also plays a critical role in many processes: removal of toxins and metabolism of fats, proteins, carbohydrates, and drugs. Chronic inflammation, trauma, or other causes of irreversible damage to the liver can dysregulate these pathways leading to organ and systemic abnormalities. In some cases, platelet-to-lymphocyte ratios can also be a predictor of disease outcome. An example is cirrhosis, which increases the risk of bleeding and prothrombotic events followed by activation of platelets. Along with a triggered coagulation cascade, the platelets increase the risk of pro-thrombotic events and contribute to cancer progression and metastasis. This progression and the resulting tissue destruction is physiologically comparable to a persistent, chronic wound. Various cancers, including colorectal cancer, have been associated with increased thrombocytosis, platelet activation, platelet-storage granule release, and thrombosis; anti-platelet agents can reduce cancer risk and progression. However, in cancer patients with pre-existing liver disease who are undergoing chemotherapy, the risk of thrombotic events becomes challenging to manage due to their inherent risk for bleeding. Chemotherapy, also known to induce damage to the liver, further increases the frequency of thrombotic events. Depending on individual patient risks, these factors acting together can disrupt the fragile balance between pro- and anti-coagulant processes, heightening liver thrombogenesis, and possibly providing a niche for circulating tumor cells to adhere to—thus promoting both liver metastasis and cancer-cell survival following treatment (that is, with minimal residual disease in the liver).

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Section: Platelet Activation and Aggregationmentioning

confidence: 60%

The Provocative Roles of Platelets in Liver Disease and Cancer

et al. 2021

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“…To further study the mechanism of THCMA inhibiting arterial thrombosis and tumor growth, 2 the antiplatelet activity of THCMA was evaluated in two ways: AFM of platelets in the presence and absence of THCMA and in vitro platelet-aggregation assay. Figure 9A shows resting rat platelets on AFM.…”

Section: Resultsmentioning

confidence: 99%

“… 1 Its overexpression occurs not only on the vascular endothelium of tumors but also on lung, ovarian, lymphoma, and breast cancer cells. 2 As an adhesion molecule, P-selectin binds with P-selectin glycoprotein ligand 1 (PSGL1), the cognate ligand expressed on leukocytes, T cells, and myeloid, lymphoid, carcinoma, and dendritic cells. 3 , 4 This binding mediates the adhesion of platelets, leukocytes, T cells, endothelial cells, and tumor cells, resulting in inflammation, thrombosis and tumor growth and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles of a New Small-Molecule P-Selectin Inhibitor Attenuate Thrombosis, Inflammation, and Tumor Growth in Two Animal Models

Feng¹,

Wang²,

Muhtar³

et al. 2021

IJN

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Purpose: To assess whether the newly designed small-molecule oral P-selectin inhibitor 3S-1,2,3,4-tetrahydro-β-carboline-3-methyl aspartyl ester (THCMA) as a nanomedicine enhances antithrombosis, anti-inflammation, and antitumor activity more than the clinical trial drug PSI-697. Methods: THCMA was designed as an amphiphile containing pharmacophores of PSI-697. Its nanofeatures were explored with TEM, SEM, Tyndall effect, ζ-potential, FT-ICR-MS, and NOESY 2D 1 H NMR. The P-selectin inhibitory effect of THCMA was demonstrated with molecular docking, ultraviolet (UV) spectra, and competitive ELISA. In vivo and in vitro assays -anti-arterial thrombosis, anti-venous thrombosis, anti-inflammation, antitumor growth, anti-platelet aggregation, rat-tail bleeding time, anticoagulation index, soluble P-selectin (sP-selectin) expression, and serum TNFα expression -were performed to explore bioactivity and potential mechanisms. Water solubility of THCMA was measured using UV-absorption spectra. Results: THCMA self-assembled into nanorings of approximately 100 nm in diameter. Its water solubility was about 1,030-fold that of PSI-697. THCMA exhibited more potent P-selectin inhibitory effect than PSI-697. The oral efficacy of THCMA was 100-fold that of PSI-697 in inhibiting arterial and venous thrombosis and tenfold in inhibiting inflammation. THCMA inhibited thrombosis at a dose that produces no coagulation disorders and no bleeding risk. THCMA exhibited enhanced antitumor activity over PSI-697 without systemic chemotherapy toxicity. THCMA significantly inhibited platelet aggregation in vitro and downregulated the expression levels of serum sP-selectin and TNFα in vivo. Conclusion:A new small-molecule P-selectin inhibitor, THCMA, has been successfully designed as a nanomedicine with largely enhanced oral efficacy compared to the clinical trial drug PSI-697, and thus might be developed for the oral treatment of arterial thrombosis, venous thrombosis, inflammation, and cancer-associated thrombosis.

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“…Platelets have an important role in cancer development, progression, and metastasis ( 117 , 119 , 130 , 131 ). Thrombocytosis has been associated with worse outcomes in several types of cancer, including lung, colorectal, ovarian, and hepatocellular carcinoma ( 132 , 133 , 134 , 135 ).…”

Section: Role Of Platelets and Antiplatelet Therapy In Cancer And Atherosclerotic Heart Diseasementioning

confidence: 99%

Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis

Leiva

AbdelHameid

Connors

et al. 2021

JACC: CardioOncology

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Cardiovascular disease and cancer are the 2 leading causes of death worldwide. Emerging evidence suggests common mechanisms between cancer and cardiovascular disease, including atrial fibrillation and atherosclerosis. With advances in cancer therapies, screening, and diagnostics, cancer-specific survival and outcomes have improved. This increase in survival has led to the coincidence of cardiovascular disease, including atrial fibrillation and atherosclerosis, as patients with cancer live longer. Additionally, cancer and cardiovascular disease share several risk factors and underlying pathophysiologic mechanisms, including inflammation, cancer-related factors including treatment effects, and alterations in platelet function. Patients with cancer are at increased risk for bleeding and thrombosis compared with the general population. Although optimal antithrombotic therapy, including agent choice and duration, has been extensively studied in the general population, this area remains understudied in patients with cancer despite their altered thrombotic and bleeding risk. Future investigation, including incorporation of cancer-specific characteristics to traditional thrombotic and bleeding risk scores, clinical trials in the cancer population, and the development of novel antithrombotic and anti-inflammatory strategies on the basis of shared pathophysiologic mechanisms, is warranted to improve outcomes in this patient population.

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Aspirin and antiplatelet treatments in cancer

Cited by 64 publications

References 140 publications

The Provocative Roles of Platelets in Liver Disease and Cancer

The Provocative Roles of Platelets in Liver Disease and Cancer

Nanoparticles of a New Small-Molecule P-Selectin Inhibitor Attenuate Thrombosis, Inflammation, and Tumor Growth in Two Animal Models

Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis

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