A lethal cancer knocked down by one-two drug punch

June 7, 2009

In the battle against cancer, allies can come from unexpected sources. Research at The Jackson Laboratory has yielded a new approach to treating leukemia, one that targets leukemia-proliferating cells with drugs that are already on the market.

Jackson Adjunct Professor Shaoguang Li, M.D., Ph.D., who now has a laboratory at the University of Massachusetts Medical School in Worcester, led a research team that identified a gene involved with the inflammatory response that could hold the key to treating or even preventing chronic myeloid leukemia (CML), a lethal cancer.

In research published in the journal Nature Genetics, the researchers also showed that an asthma medication for human patients is an effective treatment for CML in mice.

The gene, Alox5, processes essential fatty acids to leukotrienes, which are important agents in the inflammatory response. But according to the researchers, Alox5 has a more sinister side. It is vital to the development and maintenance of cancer stem cells.

Cancer stem cells are slow-dividing cells that are thought to give rise to a variety of cancers, including leukemia, and to be critical for maintaining them. Researchers theorize that cancer stem cells must be targeted for effective treatment of many cancers, but direct evidence is still lacking.

The researchers found that CML did not develop in mice without Alox5 because of impaired function of leukemia stem cells. Also, Alox5 deficiency did not affect normal stem cell function, providing the first clear differentiation between normal and cells.

Li also treated mice with CML with Zileuton, an asthma medication that inhibits the Alox5 inflammation pathway, as well imatinib, commonly known as , the most effective current leukemia medication. Imatinib effectively treated CML, but Zileuton was more effective. The two drugs combined provided an even better therapeutic effect.

The Jackson Laboratory is seeking patent protection on the novel approach to treat CML that Li and colleagues have demonstrated.

The exact mechanism for the Alox5 gene in regulating the function of leukemia stem cells but not normal stem cells needs further study, but it appears that the two types of stem cells employ different pathways for self-renewal and differentiation. The findings provide a new focus of study into how leukemia stem cells are distinct from normal stem cells and how they can be targeted in cancer therapies. A future clinical trial targeting Alox5 will provide the first anti-stem cell strategy in cancer therapy. It is likely that other cancer will have specific pathways that also differentiate them from their normal stem cell counterparts.

Source: Jackson Laboratory

Related Stories

Recommended for you

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.

Improved capture of cancer cells in blood could help track disease

March 15, 2018
Tumor cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer - even though most free-floating cancer cells will not go on to establish a new tumor.

Area surrounding a tumor impacts how breast cancer cells grow

March 14, 2018
Cancer is typically thought of as a tumor that needs to be removed or an area that needs to be treated with radiation or chemotherapy. As a physicist and cancer researcher, Joe Gray, Ph.D., thinks differently.


Adjust slider to filter visible comments by rank

Display comments: newest first

3 / 5 (2) Jun 07, 2009
Fascinating and exciting. I wish them well in their endeavors.
5 / 5 (1) Jun 08, 2009
Since these drugs are already on the market, I hope they can be put to clinical use against cancer immediately.

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.