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Biological Procedures Online

, Volume 5, Issue 1, pp 204–210

Received: 18 August 2003Revised: 08 October 2003DOI: 10.1251-bpo63

Cite this article as: Azam, M., Raz, T., Nardi, V. et al. Biol. Proced. Online 2003 5: 204. doi:10.1251-bpo63

Abstract

The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR-ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.

Indexing termsGenes, ABL Chronic myeloid leukemia Drug resistance Azam and Raz contributed equally to this manuscript.

Published: October 24, 2003

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Autor: Mohammad Azam - Tal Raz - Valentina Nardi - Sarah L. Opitz - George Q. Daley

Fuente: https://link.springer.com/







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