Drug fights lung cancer by taking away its ‘chaperone’ (VIDEO)

June 19, 2013 | by

Chaperone proteins earned their name because they help other proteins assemble, fold, stabilize and degrade in proper manner. But in cancer, they can be hijacked to maintain and promote proteins essential for tumor growth as well.

One such example is heat shock protein 90 (HSP90), a chaperone that protects other proteins from heat-related stress. It also stabilizes cancer-fueling growth factors. Now, scientists are testing to see if drugs blocking this protein can put a halt to cancer growth.

According to results of a new study, called GALAXY-1, the HSP90 inhibitor ganetespib may be promising for patients with nonsmall cell lung cancer. In this phase II trial, 252 patients with advanced disease were randomized to receive either docetaxel – a standard second-line therapy – or docetaxel plus ganetespib. They were then monitored for overall survival and progression-free survival.

Reporting their findings at the American Society of Clinical Oncology annual meeting earlier this month, the investigators found some benefit for the docetaxel-ganetespib combination compared to docetaxel alone. They also found that the benefit was greatest for patients who enrolled in the trial six or more months after their advanced lung cancer diagnosis. In this subset, those receiving the combination had a 67 percent improvement in overall survival (10.7 months versus 6.4 months) and 59 percent improvement in progression-free survival (5.4 months versus 3.4 months) compared to the docetaxel-only group.

“This is the first randomized study to demonstrate therapeutic benefit with a heat shock protein inhibitor in patients with cancer,” said the study's lead author Suresh S. Ramalingam, M.D., in an ASCO Post article. The article noted that previous HSP90 inhibitor trials have not been successful due to liver toxicity or lack of efficacy.

Commenting about the study in the video above, Marianna Koczywas, M.D., clinical professor in City of Hope's Department of Medical Oncology & Therapeutics Research, said the findings – particularly among the subset – are "very interesting."

Koczywas also said that City of Hope "will be participating in the phase III clinical trial which will answer the question if the addition of ganetespib ... to a standard dose of docetaxel will benefit patients."

In this upcoming trial, called GALAXY-2, researchers plan to assess ganetespib's efficacy specifically for people diagnosed with lung cancer six or more months earlier. Koczywas said City of Hope should start recruiting for this trial within the next month.