Investigational therapies targeting the ErbB (EGFR, HER2, HER3, HER4) family in GI cancers.

INTRODUCTION: Gastrointestinal (GI) malignancies account for nearly one-fourth of all cancer-related deaths in the United States and approximately 30% of all cancer-related deaths worldwide. Use of combination cytotoxic therapy offers a modest improvement in survival, but the prognosis and long-term survival of most patients with GI cancer remains poor. In certain GI malignancies, therapies that target members of the HER family of receptors have positively impacted patient care. AREAS COVERED: In this review, we discuss the significance of the HER family of receptors in esophagogastric, hepatobiliary, pancreatic, and colorectal cancers and explain the rationale supporting the use of monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors (TKIs) to inhibit HER activation and downstream events that contribute to tumor proliferation, migration, and survival. EXPERT OPINION: Despite recent advances, the treatment of GI cancers remains challenging. Therapies targeting the HER family of receptors have been extensively studied in these malignancies with inconsistent results. The rationale behind varied tumor responses with these agents remains uncertain. We believe that additional studies are needed to identify biomarkers that could help identify a population of patients who would be more responsive to a given therapy.