From Maria McIntire and Mark Redston: Targeted Therapies and Predictive Markers in Epithelial Malignancies of the Gastrointestinal Tract

http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2011-0167-RA

SPECIAL SECTION–PERSPECTIVES ON TARGETED THERAPIES FOR TREATMENT OF HUMAN CANCERS

Targeted Therapies and Predictive Markers in Epithelial Malignancies of the Gastrointestinal Tract

Maria McIntire, MD; Mark Redston, MD

Context.—In recent years, there has been a tremendous amount of interest in the development of targeted therapies for the treatment of human cancers. Increased understanding of the specific molecular pathways and driver mutations critical to cancer cell growth have allowed the development of these advanced therapeutics. Among these, inhibitors of the epidermal growth factor receptor and HER2/neu pathways now play a major role in the management of gastrointestinal cancers in addition to other solid malignancies. In colorectal and gastric cancers, the use of epidermal growth factor receptor inhibitors and HER2/neu inhibitors has increased the available treatment options for patients with advanced disease.

Objective.—To focus on the current targeted therapies and predictors of response in malignancies of the gastrointestinal tract.

Data Sources.—Medical literature searchable on PubMed (US National Library of Medicine) as well as older studies revealed by the literature review were used as the source of data.

Conclusion.—Gene testing of critical elements of the pathways targeted by these agents (such as KRAS mutational analysis in colorectal tumors and HER2/neu testing in gastric cancers) allows the ability to predict which patients will respond to these treatments. As the molecular profiling of tumors and our understanding of cancer genomics and epigenetic alterations continues to grow, it is expected that these personalized targeted therapies will form one of the mainstays of gastrointestinal cancer treatment.