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Table 2 Current anti-RTK therapy

From: Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges

Clinical studies of RTK-targeted therapeutics in breast cancer
Molecule Target Outcome Ref.
Gefitinib +Epirubicin and Cyclophosphamide EGFR No significance [146]
Cetuximab + Carboplatin EGFR Overall response rate: 6% (Carb), 16% (Carb + cetux), TTP - 2.1 month [148]
Cetuximab + Cisplatin EGFR Overall response rate: 10% (cis), 20% (cis + cetux) P=0.032 [149]
Cetuximab + Ixabepilone EGFR No significance [150]
Cetuximab + Irinotecan EGFR Overall response rate: 11% [151]
Panitumumab + Epirubicin, Fluorouracil and Cyclophosphamide (EFC) + Docetaxal EGFR Pathological complete response: 47% [152]
Cetuximab + Docetaxal EGFR Pathological complete response: 24% [153]
Panitumumab+Paclitaxal and Carboplatin EGFR Overall response rate: 46% [154]
Erlotinib + Bendamustine EGFR Cause excessive toxicity with severe, prolonged lymphopenia [155]
Paclitaxal + Bevacizumab VEGFR Higher progression free survival [156]
Bevacizumab + Capacitabine VEGFR Higher progression free survival [157]
Sunitinib + Docetaxal VEGFR, PDGFR No significant difference in progression free survival [158]
Currently investigated clinical trials of targeting RTK in breast cancer
Molecule Type Target Phase of study Mechanism
Trastuzumab Humanized MAb HER2 In clinical use Inhibits HFR2 and HER3 dimerization, induces ADCC [159]
Cetuximab ChimaricMAb EGFR Phase I, II Enhances sensitivity to DNA-damaging agents in BRCA1-mutated and PTEN-wild-type TNBC, Induces NK cell mediated ADCC [160, 161]
Panitumumab Humanized MAb EGFR Phase II Enhances sensitivity to DNA-damaging agents in BRCA1-mutated and PTEN-wild-type TNBC [161]
Nimotuzumab Humanized MAb EGFR Phase I Induces NK cell mediated ADCC [162]
Necitumumab Humanized MAb EGFR Phase II Inhibits downstream targets in EGFR pathway, induces ADCC [163]
Gefitinib Reversible TKI EGFR Phase I, II Reverses TAM resistance by up-regulating the ERα [164]
Erlotinib Reversible TKI EGFR Phase I, II Suppresses CDK2 activity [165]
Lapatinib Reversible TKI EGFR, HER2 In clinical use Used as an alternate therapy in trastuzumab resistant HER2 positive breast cancer [139]
Afatinib Irreversible TKI EGFR, HER2 Phase II Inhibits EGFR and HER2 signalling irreversibly [166]
Varlitinib Reversible TKI EGFR, HER2, ErbB4 Phase II Inhbits HER/MAPK signalling in TNBC [167]
Dacomitinib Irreversible TKI EGFR, HER2, ErbB4 Phase 1, Solid tumors Inhibits HER2, EGFR, HER4, Akt and ERK phosphorylation and show high antitumor effect in trastuzumab and lapatinib resistant HER2 overexpressing breast cancer [168]
Sapitinib Reversible TKI EGFR, HER2, ErbB3 Phase 1, Solid tumors Showed higher inhibitory potential in tamoxifen resistant breast cancer [169]
Vandetanib TKI EGFR, VEGFR2-3, RET Phase I, II Targets angiogenesis by inhibiting VEGFR2 and 3 signalling along with EGFR pathway [170]
Neratinib Irreversible TKI EGFR, HER2, ErbB4 Phase I, II, III Irreversibly blocks EGFR and HER2 pathway [171]
BMS-690514 Irreversible TKI EGFR, HER2, ErbB4, VEGFR1-3 Phase 1, Solid tumors Irreversibly blocks EGFR and HER2 pathway leading to inhibition of their downstream signaling pathways [172]
AEE788 Reversible TKI EGFR, ErbB2, VEGFR Phase I Targets angiogenesis by inhibiting VEGFR2 and 3 signalling along with EGFR pathway [173]
Lucitanib TKI FGFR 1-2, VEGFR 1-3, PDGFRα/β Phase II Show anti-angiogenic and anti-tumoral activity by targeting FGFR and VEGFR [174]