Incorporation of biologic therapies in the management of gastroesophageal cancers.

Gastroesophageal malignancies are highly aggressive tumors with mortality rates remaining close to incidence rates; the majority of patients have advanced incurable disease at diagnosis. Although patients receive palliative benefit from chemotherapy, 5-year survival rates remain dismally low. In the past few decades, significant progress in understanding tumor biology has led to development of therapies that target critical aspects of the oncogenic pathway. Such targets include cell growth regulators (human epidermal growth factor like receptor, Ki-67), vascular modulators (vascular endothelial growth factor), cell cycle checkpoint modulators (p16, p21, cyclin D1, cyclindependent kinases), apoptosis promoters (p53, bax, bcl-2), and cell proliferators, tissue invasion and metastasis potentiators (matrix metalloproteinase, E-cadherin, gastrin 17). Clinical assessment of the inhibition of some of these targets is under way in various tumor types, including gastroesophageal cancers. This paper reviews emerging data on selected molecular targets and their antitumor potential in gastroesophageal malignancies.