Emerging Diagnostic and Therapeutic Approaches for Gastric Cancer

Gastric cancer with liver metastasis is defined as advanced gastric cancer and remains one of the deadliest diseases with poor prognosis. Approximately 4–14% of patients with gastric cancers presented with liver metastases at the initial diagnosis. Owing to its incurability, first-line treatment for gastric cancer with liver metastases is systematic chemotherapy, whereas surgery is usually performed to alleviate severe gastrointestinal symptoms. However, continuously emerging retrospective studies confirmed the role of surgery in gastric cancer with liver metastases and showed significantly improved survival rate in patients assigned to a group of surgery with or without chemotherapy. Therefore, more and more convincing data that resulted from prospective randomized clinical trials is in need to clarify the surgery strategies in patients with gastric cancer with liver metastasis.

Despite the gradual decrease in incidence, gastric cancer is still the third leading cause of cancer death worldwide. Although chemotherapy enhances overall survival and quality of life in advanced disease, the median overall survival is < 12 months. In recent years, the human epidermal growth factor receptor (ErbB) family has been extensively investigated in gastric cancer. The ErbB family is composed of four closely-related members: ErbB-1 (HER1 or epidermal growth factor receptor, EGFR), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4), all of which play a critical role in regulating cell growth, proliferation and migration of tumors. It is well known that gastric cancer overexpresses HER in a heterogeneous pattern, especially EGFR, and HER2. HER3 is another important member of the ErbB family that preferentially activates the phosphatidylinositol 3-kinase (PI3K) pathway. Furthermore, its heterodimerization with HER2 seems fundamental for steering HER2-overexpressing breast cancer tumor growth. Less is known about the impact of HER4 on gastric cancer. Improved survival from the use of trastuzumab has paved the way for ErbB receptor family-targeted treatments in gastric cancer. However, unlike trastuzumab, ErbB receptor-targeted drugs have not consistently maintained the encouraging results obtained in preclinical and early clinical trials. This may be attributable to the intrinsic heterogeneity of gastric cancer and/or to the lack of standardized test quality for established biomarkers used to evaluate these biological targets. This review presents an overview of the most recent clinical studies on agents targeting the ErbB family in gastric cancer.