HER2 directed therapy for gastric/esophageal cancers
Elizabeth Won1, Yelena J Janjigian, David H Ilson
1Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA.
Advanced esophagogastric cancer has a poor prognosis. Trastuzumab shows promise in HER2-positive cases, improving survival, but resistance is a challenge. New therapies are under investigation.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Most esophagogastric cancer patients present with incurable advanced disease.
- Current systemic chemotherapy offers limited survival benefits, with a median overall survival less than one year.
- Molecularly targeted therapies represent a promising avenue to improve treatment outcomes.
Purpose of the Study:
- To review the role of molecularly targeted therapies, specifically HER2-targeted agents like Trastuzumab, in advanced esophagogastric cancer.
- To discuss the efficacy of Trastuzumab in combination with chemotherapy for HER2-positive metastatic gastric and gastroesophageal adenocarcinomas.
- To explore emerging therapies and resistance mechanisms in esophagogastric cancer treatment.
Main Methods:
- Review of current literature on systemic chemotherapy and molecularly targeted therapies for esophagogastric cancer.
- Analysis of clinical trial data for Trastuzumab in HER2-positive advanced gastric and gastroesophageal adenocarcinomas.
- Discussion of ongoing research into novel therapeutic strategies and resistance patterns.
Main Results:
- Trastuzumab, combined with chemotherapy, is the first molecular agent to improve response rates, time to progression, and survival in metastatic HER2-positive gastric and gastroesophageal adenocarcinomas.
- Trastuzumab is being investigated in neoadjuvant and adjuvant settings.
- Resistance to Trastuzumab is observed in esophagogastric cancer patients, similar to breast cancer.
Conclusions:
- Trastuzumab offers a significant advancement in treating HER2-positive advanced esophagogastric cancer.
- Further research is needed to overcome Trastuzumab resistance and explore new therapeutic combinations.
- Investigational therapies hold promise for improving outcomes in first and second-line settings.
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