Targeting Lung Cancer Bad Actor

ALK positive non small cell lung cancer appears to respond to investigational agent

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

(RxWiki News) In the cancer world, a protein called Hsp90 is a bad actor. It helps a number of different cancers survive and thrive. An experimental medication may become Hsp90’s worst nightmare.

A new study showed that a medicine currently in trials appeared to be able to knock out Hsp90 in people with a certain type of lung cancer.

The medication – ganetespib – also disabled another protein that's involved in lung cancer. That protein is called anaplastic lymphoma kinase (ALK).

Early studies found that ganetespib might become an effective treatment for ALK-positive non-small cell lung cancer (NSCLC).

The medicine may also help lung cancer patients who no longer respond to the only approved ALK-positive NSCLC medication – Xalkori (crizotinib).

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Synta Pharmaceuticals Corporation, the developer of ganetespib, funded a study to see if ganetespib could be an alternative to crizotinib to treat ALK-positive NSCLC.

According to the researchers, between 3 to 7 percent of NSCLC patients have a rearrangement in the coding of ALK proteins. Crizotinib is the only FDA-approved medication to treat this type of lung cancer.

While crizotinib enhances survival, most patients eventually become resistant to the medication. This medication blocks the activities of the ALK protein, which in turn kills off the cancer cells.

The investigational drug – ganetespib – targets and blocks Hsp90 (heat shock protein 90), which scientists call a “chaperone” for many cancer-related proteins, including ALK. When Hsp90 is blocked, ALK is also disabled so that cancer cells die and tumors shrink.

When working with cancer cells in the lab, researchers found ganetespib totally shut down the ALK protein. The medicine was also effective in cells that had grown resistant to crizotinib.

In mice studies, ganetespib demonstrated anti-tumor activities that resulted in the animals living longer.

Ganetespib also produced clinical response one 24-year-old male patient who had failed with crizotinib therapy.

Christopher Ruud, MD, of Austin Cancer Centers, told dailyRx News, “Crizotinib is very effective in the small proportion of patients who have ALK positive lung cancer. This new agent holds further promise for these patients.”

Ganetespib is currently being evaluated in more than 20 different clinical trials. It has not yet received FDA approval.

Findings from this study were published March 26 in Cancer Discovery, a journal of the American Association for Cancer Research.

Seven of the authors are Synta Pharmaceuticals Corp. employees. Authors disclosed various financial ties to Abbott, J-P Jimenez, Daiichi Sankyo, Novartis, Pfizer, Eli Lilly, ImClone, Boehringer Ingelheim and Insight Genetics, Inc.  The remaining author disclosed no potential conflicts of interest.

Reviewed by: 
Review Date: 
March 25, 2013
Last Updated:
March 26, 2013