Inflammatory Breast Cancer Breakthrough

ALK amplified in inflammatory breast cancer can be targeted with existing drugs

(RxWiki News) Women with inflammatory breast cancer - one of the worst forms of the disease - have reason to cheer. Scientists have made a discovery that opens the door for the treatment of this currently untreatable type of breast cancer.

Two research teams from The University of Texas MD Anderson Cancer Center and George Mason University have discovered that women with inflammatory breast cancer have an overabundance of a protein known as anaplastic lymphoma kinase (ALK). The great news is there's already an approved drug  that targets ALK, and an accelerated trial is under way to test one of them as a treatment for the most aggressive and lethal form of breast cancer.

"If you have inflammatory breast cancer, hope is here and help is on the way."

Elevated levels of ALK are also seen in other cancers, including non-small cell lung cancers. And it's now thought that this protein is the reason inflammatory breast cancer (IBC) spreads so quickly.

If validated, ALK inhibitors may become a new treatment approach for IBC, a rare form of cancer that has a very low (40 percent) five-year survival rate.

The study that identified the role of ALK was led by Fredika M. Robertson, Ph.D, professor in the department of experimental therapeutics at The University of Texas MD Anderson Cancer Center and a member of the Morgan Welch Inflammatory Breast Cancer Research Program.

Looking for both genetic abnormalities and protein signaling pathways, Robertson's team found high levels of ALK in 13 of 15 samples taken from patients. These results were validated in tumor cell lines and animal models.

These findings suggest that ALK could serve as a target for treatment. To test the theory, researchers used IBC patient tumor cells and two animal models and uncovered a drug that inhibits ALK did indeed kill tumor cells.

"There is one ALK inhibitor that was approved by the FDA this year for treatment of non-small cell lung cancer patients, and there are multiple other ALK inhibitors being evaluated,"  Robertson told dailyRx.

"This work is a collaboration with Dr. Massimo Cristofanilli, who is director of the Inflammatory Breast Cancer Clinic at Fox Chase Cancer Center in Philadelphia," Robertson said.

She continued, "He is currently evaluating IBC patients for ALK genetic abnormalities and if they are eligible, they can be enrolled into the Phase 1 open label dose escalation clinical trial for an ALK inhibitor that is open to those patients with ALK genetic abnormalities, which now includes IBC patients."

"This is especially important because IBC patients commonly have very rapid progression of their disease and there are few treatments that have been matched to the specific characteristics of inflammatory breast cancer tumors," Robertson said.

Robertson worked with a research team from George Mason University, under the direction of Emanuel "Chip" Petricoin, who is co-director of Mason's Center for Applied Proteomics and Molecular Medicine along with Lance Liotta.

The Mason team used technology Petricoin and Liotta invented called reverse phase protein array. This technology allows proteins to be physically arranged in a manner that reveals how they work on individual cells, such as cancer cells.

Moving forward, Robertson will continue to collaborate with the Mason team in using both proteomic (proteins) and genomic approaches to find therapeutic targets.

Robertson says that this study illustrates the importance of examining the role of proteins in cancer biology.

Results from this study were presented at AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics on November 13, 2011.

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Review Date: 
November 16, 2011