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Fig. 5 | Molecular Cancer

Fig. 5

From: Chronic myeloid leukemia: the paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy

Fig. 5

Overview of the mechanisms of resistance to BCR-ABL1 inhibition. According to the currently available data obtained in patients and/or cell lines, resistance may be due to (1) overexpression/increased activity of the efflux pump MDR1, and/or downmodulation/decreased activity of the influx pump hOCT1. This may result also from gene polymorphisms; (2) gene amplification and/or BCR-ABL1 mRNA and protein overexpression to levels that cannot be inhibited by achievable plasma concentrations of the TKI; (3) point mutations in the BCR-ABL1 kinase domain that interfere with TKI binding; (4) activation of alternative/downstream signaling pathways, e.g. of the SRC family kinases. Resistance mechanisms are not necessarily mutually exclusive

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