Table 1.
Effects of antiplatelet agents on tumorigenesis and metastasis formation: in vitro and in vivo studies.
| Drug Class | Drug Target | Agents | In Vivo and in Vitro Studies | Reported Effects |
|---|---|---|---|---|
| NSAIDs | Platelet COX-1 | Low-dose aspirin | In vitro co-culture of platelets and human colon adenocarcinoma cell line HT29 [29] HT29-induced hematogenous metastasis in vivo [29] In vivo mouse model of chronic hepatitis B [58] |
Prevention of platelet-induced EMT and migration (disruption of cancer cell metastatic potential) [29] Prevention of platelet-induced metastatic and prothrombotic phenotype [29] Prevention of immune-mediated liver injury and fibrosis and HCC development (in combination with clopidogrel) [58] |
| Thienopyridines | ADP receptor P2Y12 | TiclopidineTicagrerol | In vivo model of spontaneous lung metastasis [59] In vitro co-culture of platelets and HT29 colon cancer cells [29] In vitro co-culture of platelets human breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231) [60] Orthotopic 4T1 breast cancer model [60] |
Suppression of metastasis dissemination [59] Prevention of platelet-induced EMT and migration (disruption of cancer cell metastatic potential) [29] Prevention of platelet–cancer cell crosstalk [60] Reduction of metastasis formation and number of tumor cell-platelet aggregates and improvement of survival [60] |
| PAR-1 antagonists | Protease-activated receptor PAR-1 | Vorapaxar | In vitro studies with human ovarian cancer cells (SKOV-3, OVCAR-3 and CaOV-3) [61] | Reduction of PAR-1 agonist-mediated effects including cell proliferation [61] |
| Glycoprotein IIb/IIIa antagonists | Glycoprotein (GP) IIb/IIIa | AbciximabEpitifabideTirofiban | MCF-7 breast cancer cells [62] In vitro co-culture of thrombin-activated platelets and human breast carcinoma MDA-MB-231 cells [62] MCF-7 breast cancer cells [62] In vitro studies with highly invasive human tongue squamous carcinoma cell line HSC-3 [63] |
Tumorigenesis and metastasis control [62] Constriction of tumor cell invasive potential [62] Tumorigenesis and metastasis control [62] Inhibition of promigratory effect induced by Col15 [63] |
| GPIb inhibitors | Platelet GPIb | Anfibatide anti-GPIbα antibody (h6B4-Fab, GPG-290, and anti-GPIbα) |
In vitro and in vivo murine models of thrombosis [64] and phase II human clinical trials [65] High shear arterial thrombosis model in baboons [66] Canine model of artery thrombosis [67] In vivo metastasis model B16F10 melanoma cells [68] |
Inhibition of platelet adhesion, aggregation and thrombus formation, without increasing bleeding time [64,65] Reduction of thrombus formation at an injured femoral artery site [66] Prevention of coronary artery thrombosis [67] Promotion of melanoma metastasis [68] |
| P-selectin (CD62P) inhibitors | Platelet P-selectin and tumor P-selectin ligands | Anti-P-selectin antibody (GA-6), P-selectin Mab, anti-CD24 (P-selectin ligand) antibody FL80 |
Prostate cancer cell line DU145 [69] Mucin-type ligands bearingsialyl-Lewis X small-celllung cancers, colon cancer and neuroblastoma [70,71] Colon cancer cells MC-38 expressing sulfatedgalactosylceramide-typeligands [72] Murine model of gastric cancer [73] |
Prevention of platelet binding to prostate cancer cells [69] Prevention of P-selectin adhesion of platelets to cancer cells [70,71] Prevention of P-selectin-mediated metastasis progression [72] Reduction of gastric cancer metastasis [73] |
| GPVI antagonists | Platelet GPVI | Revacept | In vitro co-culture of platelets and human colon adenocarcinoma cell line HT29 [30] | Prevention of platelet-induced COX-2 upregulation and EMT [30] |
| EP3 antagonist | PGE2 receptor EP3 | DG041 | In vitro co-culture of platelets and human colon adenocarcinoma cell line HT29 [29] | Prevention of platelet-induced EMT and migration (disruption of cancer cell metastatic potential) [29] |