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The role of HER3 in gastric cancer
Liying Wang1, Hengheng Yuan1, Yanjing Li1
1Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, PR China.
Abstract:
Gastric cancer is the second leading cause of cancer mortality in the world. HER family tyrosine kinases play a critical role in the development of gastric cancer. The HER family of receptor tyrosine kinases includes EGF receptor (EGFR), HER2, HER3, and HER4. Targeted drugs antineoplastic therapies such as EGFR tyrosine kinase inhibitors have application with confrontation of gastric cancer. However, less attention has been paid to the oncogenic functions of HER3 essepecially in the gastric cancer due to its lack of intrinsic kinase activity. Recent work, however, has placed the role of HER3 in gastric cancer in the spotlight as a key signaling hub in several contexts. First, HER3 overexpression may be associated with poor prognosis and unfavorable survival mediated by PI3K/AKT signaling pathway. Second, a large amount of direct evidence has emerged the benefit of anti-HER3 agents in combination with EGFR tyrosine kinase inhibitors as well as anti-HER2 agents in gastric cancer. Furthermore, we can further elucidate the relationship between HER3 and MET inhibitors in gastric cancer that the development of resistance to MET inhibitors may result from the overexpression of HER3. This review focuses on the current achievements of the relationship between HER3 and gastric cancer in vivo and in vitro, the development of HER3 molecule-targeted therapy, additionally, the challenge which we will meet in the future.
Insights
Human Epidermal growth factor Receptor 3 (HER3) is a key signaling hub in gastric cancer, impacting prognosis and treatment. Targeting HER3 shows promise in combination therapies for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Gastric cancer is a leading cause of cancer mortality globally.
- The HER (Human Epidermal growth factor Receptor) family, including EGFR, HER2, HER3, and HER4, is crucial in gastric cancer development.
- While EGFR and HER2 are established targets, HER3's oncogenic role in gastric cancer is increasingly recognized despite its lack of intrinsic kinase activity.
Purpose of the Study:
- To review the current understanding of HER3's role in gastric cancer.
- To discuss the development of HER3-targeted therapies for gastric cancer.
- To explore the relationship between HER3, MET inhibitors, and resistance mechanisms.
Main Methods:
- Literature review of in vivo and in vitro studies on HER3 in gastric cancer.
- Analysis of clinical evidence for anti-HER3 agents in combination therapies.
- Examination of molecular pathways, including PI3K/AKT signaling and MET inhibitor resistance.
Main Results:
- HER3 overexpression is linked to poor prognosis and survival, potentially mediated by the PI3K/AKT pathway.
- Anti-HER3 agents demonstrate therapeutic benefits when combined with EGFR and HER2 inhibitors in gastric cancer.
- HER3 overexpression may contribute to resistance against MET inhibitors.
Conclusions:
- HER3 is a significant signaling hub in gastric cancer with implications for patient prognosis.
- Targeted therapies against HER3, especially in combination regimens, represent a promising avenue for gastric cancer treatment.
- Further research is needed to overcome challenges and fully leverage HER3-targeted therapies in clinical practice.
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