Unlocking Chronic Myeloid Leukemia Resistance

Tasigna plus MEK inhibitors overcomes Gleevec resistance

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Gleevec (imatinib) has transformed the treatment of chronic myeloid leukemia (CML). The problem is, this drug stops working at some point in many patients. A drug under development, combined with another currently available medication, may offer patients new options.

Researchers have discovered that combining Tasigna (nilotinib) with drugs currently in early stages of development kills CML cells that no longer respond to the standard targeted therapy, Gleevec.

"Ask your doctor about the latest drugs to treat your illness."

Researchers explain that the current drugs - Tasigna and Gleevec - work by disabling a protein that signals CML cells to stay alive. These drugs are like keys that fit into and lock this protein - BCR-ABL - from sending the survival signals to the CML cells.

Now the BCR-ABL is capable of changing its shape. When this happens, the drugs no longer fit and become powerless to keep BCR-ABL from helping CML cells to grow wildly.

All is not lost, though. Scientists have found another set of what they call "molecular keys" in drugs in early development known as MEK inhibitors. The MEK protein is the last in the line of proteins that control signals telling CML cells to survive.

Researchers learned that Tasigna makes the uncooperative cells respond to the MEK inhibitors. So this dynamic duo works together to kill the resistant cells.

This research suggests MEK inhibitors in combination with Tasigna may overcome CML resistance to single therapies of Gleevec or Tasigna.

According to Professor Richard Marais from the ICR, the study's lead author, “We are learning more about the molecular locks which have ‘seized up’, keeping survival signals turned on in CML cells. This important research shows that drugs currently in development can free these locks to switch off survival signals and destroy cancer cells," Marais said.

The next steps will involve further development of MEK inhibitors, followed by human clinical trials

This research was published December 2, 2011 in Cancer Cell.

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Review Date: 
December 14, 2011
Last Updated:
November 8, 2012