Other antiplatelet agents that may affect tumor metastasis and tumorigenesis
| Category . | Agents . | Targeting receptor–ligand interactions . | Reported tumor types . | Comments . | References . |
|---|---|---|---|---|---|
| Targeting direct molecule contacts between platelets and tumor cells | |||||
| αIIbβ3 integrin antagonists | Abciximab,* eptifibatide,* tirofiban,* RUC-4†; mAb10E5 and XV454,† anti-integrin PSI domain mAb† | Platelet αIIbβ3 integrin– plasma fibrin(ogen) or fibrin–fibronectin complex–tumor αVβ3 integrin | Melanoma, cancers of breast and likely prostate, pancreatic, ovarian, cervical; glioblastoma | αIIbβ3 is critical for bone metastasis of melanoma; activation of integrin controls metastasis in human breast cancer | 79,-81 |
| α6β1 integrin antagonists | Anti–α6-antibody GoH3† | Platelet α6β1integrin– tumor ADAM9 | Cancers of breast and colon | α6β1 promotes spontaneous and experimental lung metastasis | 82 |
| GPIbα inhibitors | Anfibatide,‡ H6B4,† NIT family mAb† | Platelet GPIbα–tumor VWF, (sub)endothelial VWF or P-selectin, leukocyte αMβ2 | Melanoma | GPIbα supports experimental lung metastasis; anti-GPIbα inhibits interactions with VWF and thrombin, which may inhibit TCIPA and tumor arrest; anti-GPIbα decreases thrombopoietin generation and may inhibit tumor-induced thrombocytosis | 91,93,119 |
| TLR4 inhibition | Anti-HMGB1† | Platelet TLR-4–tumor HMGB1 | Melanoma and lung cancer | TLR4 mediates tumor-induced platelet activation, tumor-platelet adhesion, and metastasis | 89 |
| P-selectin inhibitors | Anti–P-selectin antibody,† anti-CD24 (P-selectin ligand) antibody FL80† | Platelet P-selectin–tumor P-selectin ligands | Mucin-type ligands bearing sialyl-Lewis X on colon, prostate, small-cell lung cancers, and neuroblastoma; sulfated galactosylceramide-type ligands on colon cancer | P-selectin mediates tumor growth, metastasis, and platelet–tumor cell microthrombi | 83,,,-87 |
| CLEC-2 inhibitors | Anti-mouse CLEC-2 mAb 2A2B10† | Platelet CLEC-2–tumor podoplanin | Melanoma, brain tumors, and likely squamous cell carcinoma of the lung, head, and neck | CLEC-2 promotes hematogenous tumor metastasis and prothrombotic state; high podoplanin induces platelet aggregation, correlates with increased risk of venous thromboembolism | 71,72,90 |
| GPVI antagonists | Revacept,‡ losartan,† scFv 9012† | Platelet GPVI–tumor fibrin(ogen) and/or subendothelial collagen | Melanoma and lung cancer | GPVI deficiency is associated with a 50% reduction in experimental lung metastasis | 238,-240 |
| CD36 inhibitors | Anti-CD36 neutralizing antibody† | Platelet CD36–platelet released TSP-1–cancer cell CD36/integrins (?) | Oral squamous cell carcinoma, melanoma, breast cancer, etc | Anti-CD36 results in an antimetastatic effect; may inhibit CD36-mediated platelet activation and TCIPA | 21,74,-76,157 |
| Category . | Agents . | Targeting receptor–ligand interactions . | Reported tumor types . | Comments . | References . |
|---|---|---|---|---|---|
| Targeting direct molecule contacts between platelets and tumor cells | |||||
| αIIbβ3 integrin antagonists | Abciximab,* eptifibatide,* tirofiban,* RUC-4†; mAb10E5 and XV454,† anti-integrin PSI domain mAb† | Platelet αIIbβ3 integrin– plasma fibrin(ogen) or fibrin–fibronectin complex–tumor αVβ3 integrin | Melanoma, cancers of breast and likely prostate, pancreatic, ovarian, cervical; glioblastoma | αIIbβ3 is critical for bone metastasis of melanoma; activation of integrin controls metastasis in human breast cancer | 79,-81 |
| α6β1 integrin antagonists | Anti–α6-antibody GoH3† | Platelet α6β1integrin– tumor ADAM9 | Cancers of breast and colon | α6β1 promotes spontaneous and experimental lung metastasis | 82 |
| GPIbα inhibitors | Anfibatide,‡ H6B4,† NIT family mAb† | Platelet GPIbα–tumor VWF, (sub)endothelial VWF or P-selectin, leukocyte αMβ2 | Melanoma | GPIbα supports experimental lung metastasis; anti-GPIbα inhibits interactions with VWF and thrombin, which may inhibit TCIPA and tumor arrest; anti-GPIbα decreases thrombopoietin generation and may inhibit tumor-induced thrombocytosis | 91,93,119 |
| TLR4 inhibition | Anti-HMGB1† | Platelet TLR-4–tumor HMGB1 | Melanoma and lung cancer | TLR4 mediates tumor-induced platelet activation, tumor-platelet adhesion, and metastasis | 89 |
| P-selectin inhibitors | Anti–P-selectin antibody,† anti-CD24 (P-selectin ligand) antibody FL80† | Platelet P-selectin–tumor P-selectin ligands | Mucin-type ligands bearing sialyl-Lewis X on colon, prostate, small-cell lung cancers, and neuroblastoma; sulfated galactosylceramide-type ligands on colon cancer | P-selectin mediates tumor growth, metastasis, and platelet–tumor cell microthrombi | 83,,,-87 |
| CLEC-2 inhibitors | Anti-mouse CLEC-2 mAb 2A2B10† | Platelet CLEC-2–tumor podoplanin | Melanoma, brain tumors, and likely squamous cell carcinoma of the lung, head, and neck | CLEC-2 promotes hematogenous tumor metastasis and prothrombotic state; high podoplanin induces platelet aggregation, correlates with increased risk of venous thromboembolism | 71,72,90 |
| GPVI antagonists | Revacept,‡ losartan,† scFv 9012† | Platelet GPVI–tumor fibrin(ogen) and/or subendothelial collagen | Melanoma and lung cancer | GPVI deficiency is associated with a 50% reduction in experimental lung metastasis | 238,-240 |
| CD36 inhibitors | Anti-CD36 neutralizing antibody† | Platelet CD36–platelet released TSP-1–cancer cell CD36/integrins (?) | Oral squamous cell carcinoma, melanoma, breast cancer, etc | Anti-CD36 results in an antimetastatic effect; may inhibit CD36-mediated platelet activation and TCIPA | 21,74,-76,157 |
| Category . | Agents . | Comments . | References . | ||
|---|---|---|---|---|---|
| Targeting platelet activation pathways | |||||
| P2Y12 antagonists | Clopidogrel,* prasugrel,* ticagrelor,* cangrelor* | Coadministration of clopidogrel with aspirin markedly improves the efficacy of adoptive T-cell therapy of cancer in animal models and prevents chronic hepatitis B–associated hepatocellular carcinoma. P2Y12 deficiency results in >85% reduction in the growth of syngeneic ovarian cancer tumors; ticagrelor reduces tumor growth by 75% compared with placebo | 194,225,236 | ||
| PAR1 antagonists | Vorapaxar,* atopaxar‡ | Targeting PAR-1 is important for thrombin-enhanced metastasis | 235 | ||
| EP3 receptor antagonists | DG-041‡ | DG-041 inhibits PGE2-dependent platelet activation and aggregation and prevents platelet-mediated induction of EMT in CRC | 149,243 | ||
| Category . | Agents . | Comments . | References . | ||
|---|---|---|---|---|---|
| Targeting platelet activation pathways | |||||
| P2Y12 antagonists | Clopidogrel,* prasugrel,* ticagrelor,* cangrelor* | Coadministration of clopidogrel with aspirin markedly improves the efficacy of adoptive T-cell therapy of cancer in animal models and prevents chronic hepatitis B–associated hepatocellular carcinoma. P2Y12 deficiency results in >85% reduction in the growth of syngeneic ovarian cancer tumors; ticagrelor reduces tumor growth by 75% compared with placebo | 194,225,236 | ||
| PAR1 antagonists | Vorapaxar,* atopaxar‡ | Targeting PAR-1 is important for thrombin-enhanced metastasis | 235 | ||
| EP3 receptor antagonists | DG-041‡ | DG-041 inhibits PGE2-dependent platelet activation and aggregation and prevents platelet-mediated induction of EMT in CRC | 149,243 | ||