Gastric Cancer: New Drugs - New Strategies
#MMPMID26674336
Schulte N
; Ebert MP
; Härtel N
Gastrointest Tumors
2014[May]; 1
(4
): 180-94
PMID26674336
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BACKGROUND: Gastric cancer is the second most common cause of cancer-related
deaths worldwide. There are large geographic variations in the incidence of these
tumors, with 60% occurring in East Asia. For patients with resectable disease,
surgery and perioperative treatment can be effective. For patients with advanced
gastric cancer, chemotherapy regimens result in a median survival of 9-11 months.
In general, the prognosis for advanced disease is poor and 5-year overall
survival rates are around 15%. Combination therapies yield better survival rates,
albeit with increased toxicity. Therefore, more effective and less toxic
treatment regimens are needed. SUMMARY: The molecular aberrations that
characterize the different subgroups of gastric cancer have been used as
therapeutic targets. However, the heterogeneity and complexity of gastric cancers
is a major challenge for the development of effective targeted therapies. This
review examines the main molecular targets in the treatment of gastric cancer,
namely the vascular endothelial growth factor (VEGF), human epidermal growth
factor receptor 2 (HER2), hepatocyte growth factor (HGF)/c-Met, epidermal growth
factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)/Akt pathways. KEY
MESSAGE: The molecular aberrations characteristic of gastric cancer are being
explored for the development of targeted therapies, including the VEGF, HER2,
HGF/c-Met, EGFR and PI3K/Akt signaling pathways. PRACTICAL IMPLICATIONS:
Trastuzumab, an antibody which targets HER2, is the first approved targeted
therapy for the treatment of gastric cancer. However, trastuzumab is only
effective in HER2-positive tumors (about 10-20% of all gastric cancers).
Ramucirumab, which targets the VEGF receptor 2, has yielded benefits with respect
to overall survival in a phase III trial and is an effective treatment for
advanced gastric cancer with approval in second-line treatment. Apatinib and
rilotumumab are another two promising new agents currently under development.
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