Bypass Mechanisms of Resistance to Tyrosine Kinase Inhibition in Chronic Myelogenous Leukaemia

Title:Bypass Mechanisms of Resistance to Tyrosine Kinase Inhibition in Chronic Myelogenous Leukaemia

Volume: 11 Issue: 2

Author(s): Gabriella Marfe and Carla Di Stefano

Affiliation:

Keywords: Apoptosis, CML, imatinib, mTOR pathway, PBTDs.

Abstract: Chronic myeloid leukaemia (CML) is a disease induced by the BCR-ABL oncogene. Tyrosine kinase inhibitors (TKIs) were introduced in the late 1990s and have revolutionized the management of CML. The majority of such patients can now expect to live a normal life providing they continue to comply with TKI treatment. However, in a significant proportion of cases, TKI resistance develops over time, requiring a change of therapy. Over the past few years, multiple molecular mechanisms of resistance have been identified and some common themes have emerged. One is the development of resistance mutations in the drug target that prevent the drug from effectively inhibiting the respective TK domain. The second is activation of alternative molecules that maintain the signalling of key downstream pathways despite sustained inhibition of the original drug target.

In this mini-review, we summarize the concepts underlying resistance, the specific examples known to date and the challenges of applying this knowledge to develop improved therapeutic strategies to prevent or overcome resistance.

Cite this article as:

Marfe Gabriella and Stefano Di Carla, Bypass Mechanisms of Resistance to Tyrosine Kinase Inhibition in Chronic Myelogenous Leukaemia, Current Drug Discovery Technologies 2014; 11 (2) . https://dx.doi.org/10.2174/1570163811666140212111508