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Combining targeted therapy drugs may treat previously resistant tumors
Date:11/30/2008

A team of cancer researchers from several Boston academic medical centers has discovered a potential treatment for a group of tumors that have resisted previous targeted therapy approaches. In their Nature Medicine report, which is receiving early online release, investigators from Dana-Farber Cancer Institute (DFCI), Massachusetts General Hospital (MGH) Cancer Center, and Beth Israel Deaconess Medical Center (BIDMC) Cancer Center report that combining two different kinase inhibitors drugs that interfere with specific cell-growth pathways led to significant tumor shrinkage in mice with lung cancer driven by mutations in the K-Ras gene. In addition to their association with nearly 30 percent of cases of non-small-cell lung cancer the leading cause of cancer deaths in the U.S. K-Ras mutations are involved in many cases of colon cancer and most pancreatic cancers, which are extremely resistant to treatment.

"Finding a way to effectively treat K-Ras-mutated cancers would be a huge advance in solid tumor oncology, since these mutations are common in several incurable cancers," says Jeffrey Engelman, MD, PhD, of the MGH Cancer Center, one of the report's co-lead authors. "Cancers with K-Ras mutations have been resistant to all targeted therapies to date, and it is exciting to learn that a combination of PI3K and MEK inhibitors, two families of drugs currently in clinical development, may be highly effective in these cancers."

The current study began with a focus on the PI3K signaling pathway, which is key to cell survival and known to control cellular motility and adhesion. PI3K mutations have caused tumor development in laboratory studies, but their role had not yet been studied in an animal model. The research team developed a transgenic mouse in which administration of the drug doxycycline induces the expression of cancer-associated PI3K mutations, leading to development of lung tumors.

Treatment of those animals with
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Contact: Katie Marquedant
kmarquedant@partners.org
617-726-0337
Massachusetts General Hospital
Source:Eurekalert

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