Table 1.
Targeted therapeutics for FGFR3, HRAS and the MAPK signalling pathway
| Molecule/class | Target | In vitro effects | In vivo effects | Refs |
|---|---|---|---|---|
| SU5402/small-molecule inhibitor | FGFR3 | Inhibits growth, reduces cell viability (dose dependently), increases apoptosis in myeloma cell lines with t(4;14)(p16.3;q32) translocation | Not reported | 91 |
| SU6668/small-molecule inhibitor | FGFR3 | Inhibits tyrosine kinase ability and mitogenesis in fibroblastic and endothelial cells, respectively | Inhibits growth of glioma, melanoma, lung, colon, ovarian and epidermoid xenograft tumours; suppresses angiogenesis in glioma animal model | 94 |
| CHIR-258/small-molecule inhibitor | FGFR3 | Inhibits growth and downstream ERK signalling; produces cytotoxic and cytostatic effects (all in myeloma cell line) | Reduces tumour growth in mouse xenograft (myeloma cell line) | 89 |
| PD173074/small-molecule inhibitor | FGFR3 | Inhibits growth, reduces cell viability (dose dependently), increases apoptosis in myeloma cell lines with t(4;14)(p16.3;q32) translocation | Delays tumour progression and increases survival in a mouse model of t(4;14)(p16.3;q32) myeloma | 91, 92 |
| FGFR3 monoclonal antibody | FGFR3 | Blocks cell proliferation in multiple urothelial cancer cell lines, attenuates FGFR kinase activity in a urotheilal cell line | Suppresses urothelial and multiple myeloma tumour xenograft models | 96, 98, 99 |
| HDACI FR901228/small-molecule inhibitor | Histone deacetylase | Increases susceptibility to apoptosis in bladder and colon cancer cell lines | Not reported | 124, 125, 126 |
| HRAS antisense oligonucleotides | HRAS | Inhibits HRAS translation in a cell-free system, reduces growth of a urothelial cell line | Decreases tumourgenicity of urothelial cancer xenografts in nude mice | 121, 122, 123 |
| Farnesyl transferase inhibitors/small-molecule inhibitor | HRAS | Antiproliferative, proapoptotic, and antiangiogenic in a variety of cancer cell lines | Inhibits tumour growth in xenografts, inhibits chemically induced lung tumours, induces tumour regression and increases longevity of mice with transgene encoding mutant HRAS, potentiates effects of radiation in xenografts | 129, 130, 131, 132, 133 |
| BRAF/MEK small-molecule inhibitors | BRAF/MEK | Reduces growth, survival, invasion and angiogenesis in various cancer cell lines | Antitumourigenic in various xenograft models | 141, 142, 143, 144, 145, 146, 147 |
| BAY 43-9006/small-molecule inhibitor | BRAF | Inhibits MEK and ERK phosphorylation in various cancer cell lines with corresponding inhibition of tumour growth | Antitumour growth activity in a variety of human tumour xenograft models | 141, 142, 143 |
| CI-1040/small-molecule inhibitor | MEK | Blocks activation of MAPK in various cancer cell lines, inhibits growth on soft agar and has antiproliferative effects on colon cancer cell lines | Inhibits growth in human colon carcinoma xenografts | 144, 145 |
| ARRY-142886/small-molecule inhibitor | MEK | Same as CI-1040; inhibits MEK more efficiently | Same as CI-1040; inhibits MEK more efficiently | 147, 148 |
Abbreviations: BRAF, v-raf murine sarcoma viral oncogene homologue B; ERK, extracellular-signal-regulated (MAP) kinase; FGFR3, fibroblast growth factor receptor 3; HDAIC, histone deacetylase inhibitor; HRAS, Harvey rat sarcoma viral gene homologue; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase (MAP2K); p, short arm of chromosome; q, long arm of chromosome; t, translocation.