- Studio prognostico dei pazienti affetti da GIST
- Biologia molecolare applicata alla clinica
- I polimorfismi genici
- Imaging molecolare e ricerca preclinica nei GIST
- Monitoraggio e predittività della risposta ai farmaci a bersaglio molecolare
- Sperimentazioni cliniche
- Deep sequencing del genoma umano
- Analisi di genomica nei tumori stromali gastrointestinali (GIST)
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Letteratura sui GIST
I GIST sono stati oggetto di numerose ricerche sia precliniche che cliniche negli ultimi 10 anni. La letteratura scientifica a riguardo è numerosa. Si segnalano in questa sede solo alcuni degli studi piu' importanti che hanno cambiato radicalmente il trattamento di questi pazienti.1) DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000;231:51-8.
2) Ozguc H, Yilmazlar T, Yerci O, Soylu R, Tumay V, Filiz G, Zorluoglu A. Analysis of prognostic and immunohistochemical factors in gastrointestinal stromal tumors with malignant potential. J Gastrointest Surg. 2005;9:418-29.
3) Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, Sablinska K, Kindblom LG. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden. Cancer. 2005;103:821-9.
4) Pierie JP, Choudry U, Muzikansky A, Yeap BY, Souba WW, Ott MJ. The effect of surgery and grade on outcome of gastrointestinal stromal tumors. Arch Surg. 2001;136:383-9.
5) 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. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472-80.
6) Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364:1127-34.
7) Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342-9.
8) Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol. 2000;156:791-5.
9) Tamborini E, Bonadiman L, Greco A, Albertini V, Negri T, Gronchi A, Bertulli R, Colecchia M, Casali PG, Pierotti MA, Pilotti S. A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology. 2004;127:294-9.
10) Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG, DeMatteo RP. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. 2005;11:4182-90.
11) Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006;368:1329-38.
12) Bonvalot S, Eldweny H, Pechoux CL, Vanel D, Terrier P, Cavalcanti A, Robert C, Lassau N, Cesne AL. Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol. 2006;13:1596-603.
13) Andtbacka RH, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PW, Pollock RE, Benjamin RS, Burgess MA, Chen LL, Trent J, Patel SR, Raymond K, Feig BW. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007;14:14-24.
14) Gronchi A, Fiore M, Miselli F, Lagonigro MS, Coco P, Messina A, Pilotti S, Casali PG. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341-6.
15) Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, Fletcher CD, Demetri GD, Bertagnolli MM. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24:2325-31.
16) Miettinen M, Lasota J. Gastrointestinal stromal tumors: Pathology and prognosis at different sites. Seminars in Diagnostic Pathology. 2006; 23(2):70-83.
17) Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104.
18) Pantaleo MA, Astolfi A, Di Battista M, Heinrich MC, Paterini P, Scotlandi K, Santini D, Catena F, Manara MC, Nannini M, Maleddu A, Saponara M, Lolli C, Formica S, Biasco G. Insulin-like growth factor 1 receptor expression in wild-type GISTs: A potential novel therapeutic target. Int J Cancer. 2009 May 28.
19) M. Montemurroa, P. Schöffskib, P. Reichardtc, H. Gelderblomd, J. Schüttee, J.T. Hartmannf, R. von Moosg, B. Seddonh, H. Joensuui, C.M. Wendtnerj, E. Weberk, V. Grünwaldl, A. Rothm and S. Leyvraza. Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. European Journal of Cancer. September 2009; 45(13): 2293-2297.
20) Mussi C, Ronellenfitsch U, Jakob J, Tamborini E, Reichardt P, Casali PG, Fiore M, Hohenberger P, Gronchi A. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2009 Jul 23.
21) Rink L, Skorobogatko Y, Kossenkov AV, Belinsky MG, Pajak T, Heinrich MC, Blanke CD, von Mehren M, Ochs MF, Eisenberg B, Godwin AK.Gene expression signatures and response to imatinib mesylate in gastrointestinal stromal tumor. Mol Cancer Ther. 2009 Aug;8(8):2172-82.
22) Demetri GD, Heinrich MC, Fletcher JA, Fletcher CD, Van den Abbeele AD, Corless CL, Antonescu CR, George S, Morgan JA, Chen MH, Bello CL, Huang X, Cohen DP, Baum CM, Maki RG. Molecular target modulation, imaging, and clinical evaluation of gastrointestinal stromal tumor patients treated with sunitinib malate after imatinib failure. Clin Cancer Res. 2009 Sep 15;15(18):5902-9.
23) Guo T, Hajdu M, Agaram NP, Shinoda H, Veach D, Clarkson BD, Maki RG, Singer S, Dematteo RP, Besmer P, Antonescu CR. Mechanisms of Sunitinib Resistance in Gastrointestinal Stromal Tumors Harboring KITAY502-3ins Mutation: An In vitro Mutagenesis Screen for Drug Resistance. Clin Cancer Res. 2009 Oct 27.
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