Treatment of gastrointestinal stromal tumors with Imatinib : a major breakthrough in the understanding of the tumor-specific molecular characteristics

The therapeutic approach of this type of disease has beentransformed radically due to improved understanding of themolecular basics of carcinogenesis and the application of a specifictreatment.More than 90% of gastrointestinal tumors (GIST) are resistant toradio- and chemotherapy.These tumors arise from mesenchymal stem cells, theinterstitial cells of Cajal, which are involved in the regulation of cellmotility and exhibit surface expression of the c-kit gene, or CD117.As shown in immunohistochemical assays, c-kit gene is a proteinwith tyrosine kinase activity.Imatinib, a selective inhibitor of tyrosine kinase, has already beenused in CML (chronic myeloid leucemia), where enhanced activityof the enzyme has been observed. Treatment of GIST with Imatinibhas achieved up to 50% remission in the first trial series in 2001.Since then, over 2000 patients have undergone clinical trials allover the world, with 12 to 18 months into the trials, an objectiveresponse rate of 60 to 70%, and an improvement of outcome hasbeen shown in 80 -90% of these patients, who, up to now, had a30% survival rate at one year and a median survival time of 18months. Imatinib has not been effective in CD117 negativesarcomas. These results reflect therefore a major progress in thetreatment of solid gastrointestinal tumors, considered inoperableuntil now.