Page 116 - Read Online

Kiyozumi et al. J Cancer Metastasis Treat 2018;4:31 I http://dx.doi.org/10.20517/2394-4722.2017.77 Page 3 of 15

Figure 1. Targeted therapy and oncogenic pathways in gastric cancer. EGFR: epidermal growth factor receptor; HER: humanepidermal
growth factor receptor; HGF: hepatocyte growth factor; mTOR: mammaliantarget of rapamycin; VEGF: vascular endothelial growth factor;
VEGFR: vascular endothelial growth factor receptor

One novel antibody drug targeting HER2, trastuzumab-emtansine (TDM-1), was confirmed to be
significantly effective in breast cancer. However, a phase III study for HER2- positive GC patients added
with TDM-1 could not prolong OS and PFS during second-line treatment (GATSBY study) . The reasons
[8]
for this include the heterogeneity of HER2 expression in GC or the changed pattern of HER2 expression by
first-line chemotherapy. The detailed analyses of those results are yet to be revealed.

Tyrosine kinase inhibitors of EGFR/HER-2
Lapatinib, which is bound to the intracellular tyrosine kinase domains of epidermal growth factor receptor
(ErbB1) and HER2 (ErbB2), blocks autophosphorylation and downstream signaling. In a phase III trial,
for first-line treatment aimed at patients with HER2-positive GC, lapatinib with capecitabine + oxaliplatin
[9]
(CapeOx) showed no significant difference in OS compared with placebo + CapeOx (LOGiC study) . In
the lapatinib arm, toxicities were increased, especially diarrhea. The effect of lapatinibis was reportedly also
dependent on region and age. Although the efficiency of lapatinib plus paclitaxel has also been evaluated
in second-line treatmentfor a phase III trial, no increase in OS and PFS was observed (TyTAN trial) .
[10]
However, in patients with HER2-positive tumors or in China, clinical benefits have been shown. Therefore,
the correlations in each condition need to be examined.

Anti-EGFR monoclonal antibodies
Epidermal growth factor (EGF) is a protein that promotes cell proliferation, growth and differentiation by
binding to EGFR . Furthermore, EGFR is a transmembrane protein that activates by binding of ligands,
[11]