Targeted therapies in breast cancer: New challenges to fight against resistance

Table 1 Recapitulative breast cancer targeted therapy scheme cited in this article

Target pathway	Current therapy	Combination therapy
HER2 (HER2-positive breast cancer)	Trastuzumab/herceptin Pertuzumab lapatinib	Combination trastuzumab/lapatinib (EPHOS-B trial) trastuzumab/264RAD
m-TOR pathway	Everolimus	Possible combination everolimus/HER2 inhibitor
Angiogenesis (VEGF)	Bevacizumab paclitaxel Docetaxel	Targeting the placental growth factor and Bv8/Targeting the Notch pathway by anti-delta like ligands 4 and secretase inhibitors inhibiting simultaneously the VEGF pathway and the platelet derived growth factor receptor with a TK inhibitor
DNA repair mechanisms (TNBC) Notch-1 protein over-expression/breast cancer stem cells proliferation (TNBC)	Parp inhibitors/anthracyclins and taxanes	Possible combination cisplatin/gemcitabine/iniparib Possible combination of g-secretase inhibitor in addition to sunitinib
Immune system response Cell cycle checkpoints	Immunotherapeutic agents Antibodies against PD-1 T-cell inhibitory molecule or its ligand PD-L1	Nelipepimut-S(human leukocyte antigen)/GM-CSF Pembrolizumab in TNBC/PD-L1 positive (KEYNOTE-086 trial)

HER2: Human epidermal growth factor receptor 2; DII4: Delta like ligands 4; TNBC: Triple negative breast cancer; GM-CSF: Granulocyte-macrophage colony stimulating factor; VEGF: Vascular endothelial growth factor.