Charles D. Blanke, MD, FACP

Gastric cancer is more common than esophageal cancer in Western countries but is less fatal. More than 21,130 new cases of gastric cancer will be diagnosed in the United States in the year 2009, with 10,620 deaths expected. Worldwide, gastric cancer represents approximately 930,000 new cases and accounts for more than 700,000 deaths. The incidence and mortality of gastric cancer have been declining in most developed countries, including the United States; the age-adjusted risk (world estimate) fell 5% from 1985 to 1990.

Gastrointestinal stromal tumors (GISTs) originate from the interstitial cells of Cajal or a precursor and are the most common mesenchymal neoplasms of the gastrointestinal (GI) tract.[1] Although GISTs often present as localized masses, they are typified by a high risk of metastatic relapse, most commonly in the liver and peritoneum.

Molecularly targeted therapy isa hot topic in oncology, andthe development of imatinibmesylate (Gleevec) for gastrointestinalstromal tumors (GISTs) is one ofour best examples of the successfultranslation of basic science researchinto effective treatment of malignancy.Dr. Eisenberg has thoroughly researchedthe impetus for the use ofimatinib in GISTs and has methodicallyreviewed the results of severalcompleted trials. He broadly discussesmechanisms of resistance to the drugand talks about future directions inGIST research. Dr. Eisenberg has successfullycaptured much of the earlyexcitement surrounding the success ofimatinib, and he appropriately mentionsthe possibility of applying targetedtherapy to other solid tumors.

Both irinotecan (CPT-11, Camptosar) and paclitaxel have beenshown to have single-agent activity in adenocarcinomas of the esophagusand gastric cardia. A phase I trial of the combination at UCLAestablished the dose as irinotecan at 225 mg/m2 and paclitaxel at100 mg/m2 every 3 weeks. Preliminary data from a phase II trial of thisregimen in adenocarcinomas of the gastroesophageal junction showgood tolerability and promising activity (response rate of 27%), even inA previously treated patients.

Neoplasms of the biliary tract tree are uncommon and have a poor overall prognosis. Although numerous risk factors have been identified, little is known about the pathogenesis of these tumors, and no effective screening

Cyclooxygenase-2 (COX-2) is the enzyme that normally synthesizes prostaglandins during an inflammatory response.

Fluorinated pyrimidines have long been used as radiosensitizers in combined-modality therapy for solid tumors. Nonetheless, the most commonly used drug, 5-fluorouracil (5-FU), is inconvenient to administer, particularly