Imatinib mesylate resistance

Warmuth M, Simon N, Mitina O et al. Dual-specific SRC and ABL kinase inhibitors, PPl and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant BCR-ABL kinases. Blood 2003 101 664-672. 

Nicolini FE, Corm S, Le QH et al. Mutation status and elinieal outeome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients a retrospeetive analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia 2006 20 1061-1066. 

Kreuzer KA, Le Coutre P, Landt O et al. Pre-existence and evolution of imatinib mesylate-resistant clones in ehronie myelogenous leukemia detected by a PNA-based PCR clamping technique. Ann Hematol 2003 82 284-289. 

Walz C, Sattler M. Novel targeted therapies to overcome imatinib mesylate resistance in chronic myeloid leukemia (CML). CritRev Oncol Hematol 2006 57 145-164. 

Gorre ME, Ellwood-Yen K, Chiosis G et al. (2002) BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90. Blood 100 3041-3044... 

Shimizu T, Miyakawa Y, Iwata S et al. A novel mechanism for imatinib mesylate (STI571) resistance in CML cell line KT-1 role of TC-PTP in modulating signals downstream from the BCR-ABL fusion protein. Exp Hematol 2004 32 1057-1063. 

Ulmer T, Schaich M, Platzbecker U et al. P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 2004 18 401 08. 

Donato N, Wu J, Kong LY et al. Constitutive activation of SRC-family kinases in chronic myelogenous leukemia patients resistant to imatinib mesylate in the absence of BCR-ABL mutations a rationale use of SRC/ABL dual kinase inhibitor-based therapy (Abstract 1087). B/oo<7 2005 106 316a. 

Melo JV, Chuah C. Resistance to imatinib mesylate in chronic myeloid leukaemia. Cancer... 

Kantarjian HM, Talpaz M, O Brien S et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood 2003 101 473 75. 

La Rosee P, Corbin AS, Stoffregen EP et al. Aetivity of the BCR-ABL kinase inhibitor PDl80970 against elinically relevant BCR-ABL isoforms that eause resistance to imatinib mesylate (Gleevec, ST1571). Cancer Rei 2002 62 7149-7153. 

Houghton PJ, Germain GS, Harwood FC, Schuetz JD, Stewart CF, Buchdunger E, Traxler P (2004) Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res 64, 2333— 2337. 

Mahon FX, Belloc F, Lagarde V, Chollet C, Moreau-Gaudry F, Reiffers J, Goldman JM, Melo JV (2003) MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 101, 2368-2373. 

Breedveld P, Pluim D, Cipriani G, et al. The effect of Bcrpl (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec) implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res 2005 65 2577-2582. 

A dramatic improvement in survival was noted after the discovery of Imatinib mesylate that led to a response of 50% in patients with non-resectable GIST and to stable disease in 28% (8-9). However, it is known that not all patients respond to Imatinib mesylate and that a considerable number of patients who initially responded to the treatment may become resistant later on. PET studies with both FDG and 68Ga-Bombesin may be helpful to identify those patients with resistance early in the therapy follow-up period. 

Importantly, in a recent study, overexpression of SKI is linked to the upregulation of Bcr-Abl, leading to alterations of the balance between pro-apoptotic Ci8-ceramide and pro-survival SIP, leading to resistance to imatinib mesylate in K562 human CML cells (Baran et al., 2007). Importantly, down-regulation of SKI significantly reversed resistance to drug-induced apoptosis in these cells (Baran et al., 2007). 

Elias MH, Baba AA, Husin A, Sulong S, Hassan R, Sim GA, Wahid SEA, Ankathil R. HOXA4 gene promoter hypermethylation as an epigenetic mechanism mediating resistance to imatinib mesylate in chronic myeloid leukemia patients. Biomed Res Int 2012 2013 129715. doi 10.1155/2013/129715. 

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