Ganetespib shows potency against ALK-positive lung cancer and overcomes crizotinib resistance

A drug that indirectly impairs the function of several cancer-driving proteins, including anaplastic lymphoma kinase (ALK), may be an effective new treatment for patients with ALK—positive non-small cell lung cancer.

The drug, ganetespib, may also be effective for treating patients who have become resistant to the only FDA-approved targeted therapy for this disease, crizotinib, according to data published in Cancer Discovery, a journal of the American Association for .

"Lung cancer, a leading cause of death, is no longer thought of as a single disease, but rather as a group of diseases, each with a distinct ," according to David Proia, Ph.D., associate director of at Synta Pharmaceuticals Corporation, the company that funded the research. "This realization has paved the way for the design of new treatments tailored to the specific biological characteristics of a patient's tumor.

"For example, patients with lung cancer caused by alterations in the ALK protein typically respond well to crizotinib, which blocks that activity of the modified ALK and consequently kills off the cancer cells," said Proia. "However, as is the case for many , most patients treated with crizotinib eventually become resistant to the drug."

Proia and colleagues investigated ganetespib as an alternative treatment for ALK-positive non-small cell lung cancer (NSCLC). Ganetespib targets 90 (Hsp90), a chaperone for many different proteins, including ALK, to ensure proper functioning. When Hsp90 is blocked, ALK can no longer work properly and is destroyed by the cell. Once ALK is lost, the cancer cells die and the tumors shrink.

Ganetespib had 30 times greater potency than crizotinib against a cultured ALK-positive NSCLC cell line, resulting in the complete loss of ALK . In addition, the drug was active against ALK-positive lung cancer cell lines that had become resistant to the effects of crizotinib.

The researchers then compared ganetespib and crizotinib in mice xenografted with human ALK-positive NSCLC . Ganetespib displayed greater antitumor activity and prolonged animal survival as compared to crizotinib. It was also shown that ganetespib had meaningful activity in a patient with ALK-driven NSCLC who had responded to, and then progressed, following crizotinib therapy.

"Ganetespib therapy represents a new option for treating ALK-dependent lung cancer in sequence with direct ALK inhibitors and/or for treating patients who relapse following direct ALK inhibitor therapy," said Proia.

Related Stories

Study examines drug resistance in ALK positive lung cancer

date Jan 19, 2012

Scientists from the University of Colorado Cancer Center have once again advanced the treatment of a specific kind of lung cancer. The team has documented how anaplastic lymphoma kinase (ALK) positive advanced non-small cell ...

Recommended for you

Breast cancer is not one disease, experts say

date 11 hours ago

(HealthDay)—Breast cancer isn't the same for every woman, even at the cellular level, according to a new statement from four major medical groups focused on the disease.

Teens with breast lumps may be able to avoid invasive biopsy

date 13 hours ago

If a lump is found in the breast of an adolescent girl, she often will undergo an excisional biopsy. However, breast cancer is rare in adolescents, and the vast majority of teenage breast lumps turn out to be benign masses ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.