Table II.
Inhibitors or antibodies for signaling pathway elements in breast cancer.
| No. | Target | Target agents | Refs. |
|---|---|---|---|
| 1 | HER2 | Trastuzumab (Herceptin); pertuzumab (Omnitarg); CP-724,714; TAK165; CI-1033; 2C4; AG1478; ARRY-380 | (113,118–120) |
| EGFR/HER2 | Lapatinib (Tykerb); AEE-788; BMS-599626; ARRY-334543; BIBW2992; HKI-272; MP-412; CI-1033 (canertinib); neratinib (HKI-272); CUDC-101; AZD8931; BMS-599626; ARRY-334543; dacomitinib (PF-00299804); TAK-285 | (113,121–128) | |
| EGFR | Gefitinib (ZD-1839, Iressa); CPI-358,774; cetuximab; OSI-774; PD153035; erlotinib | (118, 129, 130) | |
| VEGFRs | Regorafenib (BAY 73-4506)a; BAY 43-9006; OSI-930; SU11248b; axitinib (AG-013736); cediranib (AZD2171); vandetanib (Zactima, ZD6474); motesanib diphosphate (AMG-706); E7080 (lenvatinib); ENMD-2076; telatinib (BAY 57-9352); linifanib (ABT-869); apatinib (YN968D1)c; cabozantinib (XL184); RAF265 (CHIR-265) | (71,131–144) | |
| EGFR/VEGFRs | AEE-788; EXEL-7647 (XL647) | (113,145) | |
| 2 | FGF | 1A6; FP-1039; palifermin (Kepivance) | (146) |
| 3 | FGFRs | SU5402; PD173074; TKI-258; BIBF 1120; BMS-582,664 (brivanib); E7080; TSU-68; IMC-A1; PRO-001; R3Mab; AZD-4547; ENMD-2076; AZD4547 | (84,139,146,147) |
| 4 | IGF-1R | BMS-754807; NVP-AEW541 | (84,148) |
| IGF-1R/IR | Cixutumumab; MK-0646; dalotuzumab; CP-758171; BMS-554417; BMS-536924; GSK1904529A; OSI-906 (linsitinib); AG-1024 (Tyrphostin); GSK1838705A | (84,125,149–152) | |
| 5 | ER | ICI 182,780; tamoxifen; Casodex; fulvestrant; letrozole; anastrozole; exemestane | (60,153,154) |
| 6 | PI3K | Wortmannin; BKM120; LY294002; XL-147; GDC-0941; PX-866; ZSTK474; SF1126; IC486068; fused heteroaryl and imidazopyridine-based inhibitors; WAY-266176; WAY-266175; PIK75 | (60,84,111,129,153, 155–157) |
| PI3K/mTOR | BEZ235; XL-765; GSK2126458; PKI-402; GDC-0980; PF-05212384 (PKI-587) | (60,84,158–161) | |
| 7 | AKT | MK-2206; PX-316; perifosine (KYX-0401); UCN-01; GSK690693; AT7867; PHT-427; triciribine | (84,129,162–165) |
| 8 | PDK1 | OSU-03012; PHT-427; BX-795; BX-912; BX-320; | (129,164,166) |
| 9 | mTORC1 | Everolimus; rapamycin; RAD-001; temsirolimus (CCI-779); ridaforolimus (AP23573; MK-8669); PF-04691502; | (60,167–170) |
| mTORC1/2 | OXA-01; OSI-027; AZD8055; WYE-125132 (WYE-132); GSK2126458; GDC-0980; WAY-600; WYE-687; WYE-354; AZD2104; IKK-128; XL388 | (133,158,171–176) | |
| 10 | Raf | Regorafenib (BAY 73-4506)b; sorafenib (BAY 43-9006, Nexavar); RAF265 | (131,132,144) |
| 11 | MEK1/2(MAPK) | UO126; PD98059; CI-1040 (PD184352); UCN-01; PD318088 | (119,153,156,177,178) |
Regorafenib (BAY 73-4506) is an oral multikinase inhibitor of of VEGFR1/2/3, PDGFRβ, KIT, RET and Raf-1 (131).
SU11248, an oral multitargeted TKI with antiangiogenic and antitumor activity, inhibits VEGF, PDGF, KIT and FLT3 receptor TKs (70).
Apatinib (YN968D1) is a small-molecule TKI that inhibits VEGFR2 (Flk-1/KDR), RET (rearranged during transfection), c-Kit (stem cell factor receptor) and c-Src tyrosine kinases (142).
HER, human epidermal growth factor receptor; ER, estrogen receptor; EGFR, epidermal growth factor receptor; VEGFR, vascular endothelial growth factor receptor; FGF, fibroblast growth factor receptor; IGF, insulin-like growth factor; PI3K, phosphatidylinositol-3-kinase; mTOR, mammalian target of rapamycin; PDK, phosphoinositide-dependent kinase; MAPK, mitogen-activated protein kinase; PDGFR, platelet-derived growth factor receptor; FLT, FMS-like tyrosine kinase; TKI, tyrosine kinase inhibitor.