Tarčno zdravljenje razsejanih gastrointestinalnih stromalnih tumorjev v Sloveniji Targeted treatment of metastatic gastrointestinal stromal tumors in Slovenia.

Abstract

Gastrointestinalni tumorji (GIST) so redke neoplazme mezenhimskega izvora, ki na celični površini izražajo transmembranski receptor KIT, produkt c-kit protoonkogena. Pri patogenezi GIST so pomembne mutacije KIT. Njihova posledica je aktivacija KIT signalne poti, ki vodi do nekontrolirane proliferacije celic in rezistenco na apoptozo. Do nedavnega je bilo radikalno kirurško zdravljenje edina uspešna oblika zdravljenja za manjše in dobro omejene GIST, za razsejano bolezen pa ni bilo uspešne terapije. Z odkritjem imatinib mesilata in kasneje sunitiniba, ki inhibirata KIT signalno pot, se je prognoza bolnikov z GIST močno izboljšala. Srednje preživetje bolnikov z razsejano boleznijo se je iz pol leta povečalo skoraj na pet let. Od leta 2001 smo na Onkološkem inštitutu Ljubljana uspešno zdravili 51 bolnikov. Srednje preživetje naših bolnikov je 66 mesecev. To lahko pripisujemo timski obravnavi bolnikov, ki je glede na velikost Slovenije in nizko incidenco GIST smiselna na enem mestu.

Abstract (Eng)

Gastrointestinal stromal tumors (GIST) are rare mesenchymal neoplasms. They express the cell-surface transmembrane receptor KIT, a product of the c-kit proto-oncogene. Frequent mutations of KIT result in the constitutive activation of KIT signaling, which leads to uncontrolled cell proliferation and resistance to apoptosis. Until recently, surgery was the only successful treatment for localized GIST, while there was no effective treatment for metastatic disease. With the discovery of imatinib mesylate and sunitinib, selective inhibitors of certain protein tyrosine kinases, the prognosis of unresectable or metastatic GIST has substantially improved from a median survival of 6 months to almost 5 years. From 2001, we have successfully treated 51 patients with GIST at the Institute of Oncology Ljubljana. Median survival of our patients is 66 months. This treatment success can be attributed to the fact that all Slovenian metastatic GIST patients were treated by the multidisciplinary sarcoma team at our institution, which is, for a small country as Slovenia, a rational approach to the management of a rare disease.