Abstract
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. This tumor is resistant to conventional chemotherapy and radiotherapy. Although surgery has been the only effective treatment for GIST to date, it is not enough to manage metastatic GIST. Imatinib mesylate, a KIT tyrosine kinase inhibitor, is an oral agent that has been found to have a dramatic antitumor effect on metastatic GIST with either wild-type or mutant KIT. Although imatinib mesylate has been used in GIST treatment for several years, its use marks a new era of molecular targeting therapy. While several issues remain, they should be clarified by the current clinical trials and associated laboratory studies.
Similar content being viewed by others
References
Benjamin RS, Rankin C, Fletcher F, Blanke C, Von Mehren M, Maki R, Bramwell V, Baker L, Borden E, Demetri GD, for the Sarcoma Intergroup (2003) Phase III dose-randomized study of imatinib mesylate (STI571) for GIST: Intergroup S0033 early results (abstract 3271). Proc Am Soc Clin Oncol 22:814
Caletti G, Zani L, Bolondi L, Brocchi E, Rollo V, Barbara L (1989) Endoscopic ultrasonography in the diagnosis of gastric submucosal tumor. Gastrointest Endosc 35:413
DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF (2000) Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231:51
Dematteo RP, Heinrich MC, El-Rifai WM, Demetri G (2002) Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol 33:466
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472
Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O’Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW (2002) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 33:459
Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ (2000) Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96:925
Heinrich MC, Blanke CD, Druker BJ, Corless CL (2002) Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 20:1692
Heinrich MC, Rubin BP, Longley BJ, Fletcher JA (2002) Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 33:484
Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, Silberman S, Capdeville R, Dimitrijevic S, Druker B, Demetri GD (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052
Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM (1998) Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259
Matsui M, Goto H, Niwa Y, Arisawa T, Hirooka Y, Hayakawa T (1998) Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors. Endoscopy 30:750
Miettinen M, Sobin LH, Sarlomo-Rikala M (2000) Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol 13:1134
Mudan SS, Conlon KC, Woodruff JM, Lewis JJ, Brennan MF (2000) Salvage surgery for patients with recurrent gastrointestinal sarcoma: prognostic factors to guide patient selection. Cancer 88:66
Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM (1992) Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg 215:68
Rösch T (1992) Endoscopic ultrasonography. Endoscopy 24:144
Rossi CR, Mocellin S, Mencarelli R, Foletto M, Pilati P, Nitti D, Lise M (2003) Gastrointestinal stromal tumors: from a surgical to a molecular approach. Int J Cancer 107:171
Rubin BP, Fletcher JA, Fletcher CD (2000) Molecular insights into the histogenesis and pathogenesis of gastrointestinal stromal tumors. Int J Surg Pathol 8:5
Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M (1998) CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 11:728
Sircar K, Hewlett BR, Huizinga JD, Chorneyko K, Berezin I, Riddell RH (1999) Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 23:377
Tio TL, Tytgat GNJ, den Hartog Jager FCA (1990) Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience with 42 cases. Gastrointest Endosc 36:342
Tuveson DA, Willis NA, Jacks T, Griffin JD, Singer S, Fletcher CD, Fletcher JA, Demetri GD (2001) STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 20:5054
van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (2001) Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 358:1421
Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, Radford J, Le Cesne A, Hogendoom PC, di Paola ED, Brown M, Nielsen OS (2003) Imatinib mesylate (STI-571) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target: results from the EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer 39:2006
von Mehren M, Blanke C, Joensuu H, Heinrich MC, Roberts P, Eisenberg B, Silberman S, Dimitrijevic S, Kiese B, Fletcher J, Fletcher C, Demetri GD (2002) High incidence of durable responses induced by imatinib mesylate (Gleevec) in patients with unresectable and metastatic gastrointestinal stromal tumors (GISTs) (abstract 1608). Proc Am Soc Clin Oncol 21:403a
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was presented at the 19th Bristol-Myers Squibb Nagoya International Cancer Treatment Symposium, “State of the Arts for Digestive Organs”, 14–15 November 2003, Nagoya, Japan.
Rights and permissions
About this article
Cite this article
Sawaki, A., Yamao, K. Imatinib mesylate acts in metastatic or unresectable gastrointestinal stromal tumor by targeting KIT receptors—a review. Cancer Chemother Pharmacol 54 (Suppl 1), S44–S49 (2004). https://doi.org/10.1007/s00280-004-0886-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-004-0886-y