A decade has gone by since the initial excitement about this “dream come true” story of Imatinib in GIST, which has clearly become a poster child of targeted therapy for solid tumors. The bar was set high, many lessons have been learned and a whole host of new questions have emerged. We now know that patients with metastatic GIST do indeed enjoy a longer life span, generally with a very acceptable quality of life on long-term Imatinib. But unfortunately, development of secondary resistance is fairly universal. The main reason for this resistance appears to be the development of secondary mutations, which then requires dose optimization and alternative kinase inhibitors with much limited success than seen with front-line therapy. While the attempts at identifying more potent and broad-spectrum inhibitors addressing these secondary mutations continue, early diagnosis and appropriate institution of multimodality therapy needs to be emphasized to enhance the outcomes for patients with GISTs. It is therefore of paramount importance that the gastroenterologists and general surgeons who may be the initial consultants for these patients be aware of this entity and communicate closely with the pathologists to establish the correct diagnosis. Risk assessment models incorporating the known prognostic factors are available to the oncologists that would then help predict the risk of recurrence and discuss the role of adjuvant Imatinib with individual patients.

The primary objective of this special issue dedicated to GISTs is to engage all the disciplines likely to be involved in the diagnosis and care of these patients. Experts in the field review the lessons learned over the last ten years in the adjuvant, neoadjuvant and advanced disease settings. Some of the preliminary data on blood level testing and its implications are addressed. Finally, emerging data on mutational analysis, resistance and newer kinase inhibitors are reviewed. It is our sincere hope that this will be a useful and educational reference for our colleagues in various diagnostic and therapeutic disciplines.