Open Access

A screen to identify drug resistant variants to target-directed anti-cancer agents

  • Mohammad Azam1,
  • Tal Raz1,
  • Valentina Nardi1,
  • Sarah L. Opitz1 and
  • George Q. Daley1Email author
Biological Procedures Online5:51204

Received: 18 August 2003


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 terms

Genes, ABLChronic myeloid leukemiaDrug resistance