Table 3.
List of specific pathways relevant for platelet effects on tumor growth, respective receptors and ligands as well as candidate drugs to target those.
| Target Type | Receptor | Ligand | Pathway | Drug |
|---|---|---|---|---|
| ADHESION RECEPTORS | ||||
| Platelet A | GPIa/IIa (α2β1) | Collagen | FAK/f-actin, Rac1/p38/MAPK | Secretion |
| GPVI | Collagen | CaM/Lyn/Syk/SLP76/Btk/PI3K/PLCγ2 | RevaceptC | |
| GPIb, (GPIX,GPIbβ,GPI bα,GPV complex) | vWF | FAK/F-actin, CaM/Lyn/Syk/SLP76/Btk/PI3K/PLCγ2 | GSK2256098C, PF-562271PC, DefactinibC, PF-573228PC, Y15 & Y11PC, CEP37440PC | |
| GPIIb/IIIa (αIIb/β3) | Fibrinogen | FAK/CIB-1/actin, ARP 2/3/actin Polymerization, FAK/Paxillin/RhoGEF | AbciximabC, EptifibatideC, TirofibanC, XV454PC | |
| αv/β3 | Vitronectin | c-Src, FAK, Paxillin, PI3K | SB-273005PC, SC-68448C, EMD121974C, vitaxinC | |
| Signal Transduction | ROCK | Rho Kinase activity | Y27632PC | |
| Myosin II | ATPase activity | BlebbistatinPC | ||
| CLEC-2 | Podoplanin | Syk/PLCγ2 | 2CPPC, Mabs | |
| P-Selectin | Mucins, P-,E-,L-Selectins | Shc·Grb2·Sos1 | RivipanselC, CrizanlizumabC, HeparinsC | |
| EICOSANOID PATHWAY | ||||
| Resting Platelet | IP, Prostacyclin receptor Agonists | PGI2 | GPCR/αGs/adenylate cyclase/cAMP | IloprostC, TreprostinilC, SelexipagC |
| PDE3-PDE5 | cAMP | Phosphodiesterase activity | CilostazolC, DipyridamoleC, | |
| Platelet B | TP, Thromboxane A2 receptor Antagonists | TxA2 | GPCR/G12/13/RhoGEF/Rho/ROCK/LIMK/Cofilin/actin MLCK/Myosin | TerutrobanPC, DaltrobanPC, PicotamideC, SulotrobanPC, CAY10535PC, IfetrobanC, SQ29548PC, BM 567PC, Pinane TXA2PC |
| Thromboxane Synthase (TXAS) Inhibitors | TxA2 | AA-2O2/COX-1 /PGG2/PGH2/TXAS/ TxA2 | OKY-046C, RidogrelC | |
| Cyclooxygenase 1 (COX-1) | AA-2O2 | AA-2O2/COX-1 /PGG2/PGH2 | AspirinC, ASP6537PC, SC560PC, FR122047PC, MofezolacPC, FluorofuranonesPC | |
| EP3 Prostaglandin E2 receptor Antagonist | PGE2 | GPCR/Gαq/PLCγ/P/IP2/IP3/IP3-R/Ca+2 release/DAG/PKC/CalDAGGEF1/Rap1B/RIA M/actin | DG 041PC | |
| 12-lipoxygenase (12-LOX) Inhibitors | 12-HETE | AA-O2/12-LOX/12-HETE | ML355PC, NCTT-956 | |
| GPCR | ||||
| Platelet C | PAR1 Antagonist | ADP | GPCR/Gq/RhoGEF/Rho/ROCK/LIM-K/Cofilin/actin/MLCK/Myosin, β-arrestin | VoraxoparC, CH 79797C, RWJ 56110PC |
| P2Y1 Receptor Antagonists | ADP | GPCR/Gαq/PLCγ/P/IP2/IP3/IP3-R/Ca+2 release/DAG/PKC/CalDAG-GEF1/Rap1B/RIAM/actin | A2P5PPC, A3P5PPC, MRS2179PC, MRS2500PC | |
| P2Y12 Receptor Antagonists | ADP | Gai2/AC | ClopidogrelC, TiclopidineC, PrasugrelC, TicagrelorC, CangrelorC, ElinogrelC | |
| 5HT2A Receptor Antagonists | Serotonin (5-hydroxy tryptamine) | GPCR/Gαq/PLCγ/P/IP2/IP3/IP3-R/Ca+2 release/DAG/PKC/CalDAG-GEF1/Rap1B/RIAM/actin | TemanogrelC, NaftidrofurylC, SarpogrelatC, AT-1015PC |
PC: preclinical, C: clinical