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Esophageal carcinoma: are modern targeted therapies shaking the rock?
Patrick M Boland1, Barbara Burtness
1Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Purpose Of Review:
Our current review aims to outline recent progress in the development of modern targeted therapeutic regimens for esophageal cancer.
Recent Findings:
Esophageal cancers demonstrate marked molecular heterogeneity. Modern technology increasingly allows us to identify subgroups of patients whose tumors fit particular molecular profiles. Tumor-based human epidermal growth factor receptor 2 (HER-2) analysis has become a standard part of the work-up for patients with tumors of the esophagogastric junction. The anti-HER-2 antibody, trastuzumab, when added to a chemotherapeutic regimen combining a fluoropyrimidine and platinum, provides a survival benefit for those patients with HER-2 overexpression and/or amplification. Despite large coordinated efforts to establish the efficacy of additional targeted therapeutics, to this point minimal additional benefit has been realized in affecting prominent molecular targets, such as vascular endothelial growth factor and epidermal growth factor receptor, in esophageal cancer. Multiple targets of interest remain under investigation with some early encouraging data. These targets include mammalian target of rapamycin, c-MET, insulin like growth factor 1 receptor and cytotoxic T-lymphocyte antigen 4. Additional improvements in therapy may stem from improved patient selection for combinations of standard cytotoxic regimens, such as platinum-based regimens.
Summary:
Targeted therapeutics have yielded early benefit, but further progress will require a deeper understanding of this disease, improved identification of subpopulations who may derive greater benefit, and continued multicenter efforts to conduct the necessary clinical investigations.
Insights
Targeted therapies show promise for esophageal cancer, with human epidermal growth factor receptor 2 (HER-2) targeted treatments improving survival. Further research is needed to identify patient subgroups benefiting from other targeted agents.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Esophageal cancer exhibits significant molecular heterogeneity.
- Advancements in technology enable identification of patient subgroups with specific molecular profiles.
- Targeted therapies aim to exploit these molecular differences for improved treatment outcomes.
Purpose of the Study:
- To review recent advancements in targeted therapeutic regimens for esophageal cancer.
- To highlight the role of molecular profiling in guiding treatment decisions.
- To discuss the efficacy and challenges of current and emerging targeted therapies.
Main Methods:
- Review of current literature on targeted therapies in esophageal cancer.
- Analysis of molecular profiling techniques, including human epidermal growth factor receptor 2 (HER-2) testing.
- Evaluation of clinical trial data for targeted agents and combination therapies.
Main Results:
- Human epidermal growth factor receptor 2 (HER-2) targeted therapy (trastuzumab) combined with chemotherapy improves survival in HER-2 positive esophageal cancers.
- Targeting other molecular pathways like vascular endothelial growth factor and epidermal growth factor receptor has shown limited success to date.
- Investigational targets include mammalian target of rapamycin, c-MET, insulin-like growth factor 1 receptor, and cytotoxic T-lymphocyte antigen 4, with early promising data.
Conclusions:
- Targeted therapeutics have demonstrated initial benefits in esophageal cancer treatment.
- Further progress necessitates a deeper understanding of the disease's molecular landscape.
- Improved patient selection and continued multicenter clinical investigations are crucial for advancing targeted therapy efficacy.
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