RESUMEN
Improvements in the understanding of molecular oncogenesis and mechanisms of drug resistance have presented new opportunities for the treatment of gastrointestinal stromal tumors (GIST). In particular, the discovery of c-kit genomic mutations in GIST and the development of targeted therapy with imatinib mesylate and sunitinib have heralded a new era in the treatment of this disease. Due to its high activity in GIST, imatinib has become the standard of care in treating both advanced disease and localized disease with high-risk features. On the other hand, these developments have provided new challenges in optimizing the use of our drug armamentarium in conjunction with surgery. This review focuses on the molecular oncogenesis of GIST and provides a summary of recent approaches in the management of this disease.
RESUMEN
Although the incidence of gastric cancer has been declining in the United States, the disease continues to pose a devastating problem worldwide. Complete surgical resection offers the only chance of cure for localized gastric cancer. The recommended extent of surgical lymphadenectomy has been debated for some time, but no consensus has emerged. Unfortunately, local and distant recurrence are frequent, and long-term survival remains low. Randomized adjuvant chemotherapy trials have shown mixed results, with no consistent overall survival benefit. The Gastric Cancer Intergroup Trial 0116 demonstrated that adjuvant chemoradiotherapy with 5-fluorouracil/leucovorin significantly improves disease-free and overall survival. More recently, the MAGIC trial showed a survival benefit with perioperative chemotherapy. Preoperative (neoadjuvant) chemotherapy and chemoradiotherapy have also been explored in phase II studies, with encouraging results; however, the potential benefits of these approaches need to be assessed in phase III trials. Biologic agents are beginning to be incorporated into multimodality treatment and have shown promising results thus far.