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Met, IGF1R, and other new targets in upper GI malignancies
Elizabeta C Popa1, Manish A Shah
1Division of Hematology and Medical Oncology, Weill Cornell Medical College, 1305 York Avenue 12th floor, New York, NY, 10021, USA, ecp2002@med.cornell.edu.
Opinion Statement:
Upper gastrointestinal (GI) malignancies comprise some of the most aggressive human cancers. Expanding knowledge of molecular mechanisms is finally translating into clinical application, and this has occurred at a relatively rapid rate in the past several years. However, despite recent advances in targeted therapies in upper GI cancers our overall success with targeted therapeutics in this disease area remains dismal. This statement is particularly troubling given some sobering facts: upper GI malignancies are prevalent as well as aggressive with a high morbidity and mortality. Esophagus and gastric cancer combined have an annual global incidence of over 1.2 million new cases annually while median survival is less than 1 year for most patients with metastatic disease. Progress has been limited due to several factors including: disease heterogeneity and variance of phenotype across the globe, clinical trial design strategies that have not yet incorporated selective mechanisms to afford individualized matching of drug to tumor molecular profile and last, a lack of validated predictive markers. Nevertheless there is evidence that many targeted agents can be administered safely at doses that achieve the required effect at the protein level. Several drugs that have negative early trial results can be potentially vital therapeutic agents if patient selection is appropriate.
Insights
Targeted therapies show limited success in aggressive upper gastrointestinal (GI) cancers. Improved patient selection based on molecular profiles is crucial for effective treatment of esophageal and gastric cancers.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Upper gastrointestinal (GI) malignancies, including esophageal and gastric cancers, are aggressive and prevalent, leading to high morbidity and mortality.
- Despite recent advances in molecular biology, targeted therapies have shown dismal success rates in these cancers, with median survival less than one year for metastatic disease.
Purpose of the Study:
- To highlight the limitations of current targeted therapy approaches in upper GI cancers.
- To emphasize the need for improved strategies, including individualized patient selection and validated predictive markers, to enhance treatment efficacy.
Main Methods:
- This opinion statement synthesizes current knowledge on targeted therapies for upper GI malignancies.
- It reviews factors contributing to limited clinical success, such as disease heterogeneity and suboptimal clinical trial designs.
Main Results:
- Current targeted therapeutics in upper GI cancers have yielded limited success.
- Many targeted agents can be safely administered at effective protein-level doses.
- Negative early trial results may be overcome with appropriate patient selection.
Conclusions:
- Progress in treating upper GI cancers is hindered by disease heterogeneity, lack of individualized treatment matching, and absence of validated predictive markers.
- Optimizing patient selection based on molecular profiles holds potential for improving the efficacy of targeted agents in esophageal and gastric cancers.
- Further research into predictive markers and refined clinical trial designs is essential for advancing targeted therapy in upper GI malignancies.
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