Current status of novel agents in advanced gastroesophageal adenocarcinoma
Nishi Kothari1, Khaldoun Almhanna1
1Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Abstract:
Gastroesophageal (GE) adenocarcinomas are highly lethal malignancies and despite multiple chemotherapy options, 5-year survival rates remain dismal. Chemotherapy is the mainstay of treatment but patients are often limited by toxicity and poor performance status. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and develop targeted therapies that act on individual tumors. Trastuzumab, a human epidermal growth factor receptor type 2 (HER2) monoclonal antibody, was the first such agent shown to improve response rate, progression free survival (PFS), and overall survival (OS) when added to cisplatin based chemotherapy in patients with HER2 over-expressing GE junction (GEJ) and gastric adenocarcinomas. However, HER2 over expressing GE tumors are in the minority and the need for additional targeted agents is urgent. Though many agents are in development, incorporating targeted therapy in the treatment of GE cancers comes with a unique set of challenges. In this review, we outline oncogenic pathways relevant to GE adenocarcinomas, including HER2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and c-Met, and discuss recent trials with agents targeting these pathways.
Insights
Gastroesophageal adenocarcinomas are lethal, with poor survival despite chemotherapy. Targeted therapies addressing molecular pathways like HER2 offer promise but face challenges, necessitating further research into agents for these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gastroesophageal (GE) adenocarcinomas are aggressive cancers with low survival rates.
- Current chemotherapy treatments are limited by toxicity and patient performance status.
- Tumor molecular heterogeneity necessitates personalized treatment strategies.
Purpose of the Study:
- To review oncogenic pathways implicated in GE adenocarcinomas.
- To discuss targeted therapies for GE cancers.
- To highlight challenges in developing and implementing targeted treatments.
Main Methods:
- Literature review of oncogenic pathways in GE adenocarcinomas.
- Analysis of recent clinical trials involving targeted agents.
- Discussion of therapeutic strategies targeting HER2, EGFR, VEGF, FGF, HGF, and c-Met.
Main Results:
- Trastuzumab demonstrated efficacy in HER2-overexpressing GE cancers.
- HER2-overexpressing tumors represent a minority of GE adenocarcinomas.
- Numerous targeted agents are under development for GE cancers.
Conclusions:
- Targeted therapies are crucial for improving outcomes in GE adenocarcinomas.
- Addressing molecular heterogeneity is key to developing effective treatments.
- Ongoing research into novel targeted agents and strategies is urgently needed.
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