Two novel drugs kill breast cancer tumor cells

August 28, 2015

The findings, published online in the journal Cancer Biology and Therapy, may also have implications for prostate cancer, lymphoma, myeloma and other hematologic cancers.

Paul Dent, Ph.D., associate professor of biochemistry and radiation oncology, led the team. This new study translates its 2002 research that showed early success in the lab and more recently was tested in animals.

In this new study, researchers combined two novel drugs, UCN-01 and a MEK 1/2 inhibitor, which are known to inhibit protein kinases, part of tumor survival signaling pathways.

"In addition to potently inhibiting cells and suppressing tumor growth, these drugs are also part of a modern class of drugs that are less toxic to non-cancerous cells," said Dent. "We are eager to move these exciting findings from the labs to patients."

When studied separately, the drugs only killed a small percent of the cells to which they were exposed. Combined, however, the result was quite startling.

"Within five days, we saw profound tumor cell death," Dent said. "Three researchers in the group operated the same studies independently, and they all saw very similar results."

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In other words, he says, while a majority of cancer cells will die, those that are able to escape death will be left with a far stronger ability to metastasize and spread to other parts of the body.

"This paper is important because it shows that a pathway known to be involved in initiating breast cancer, the PI3K/AKT pathway, also plays a paradoxical role in suppressing the ability of the tumor to invade new tissues," says Lewis Cantley, PhD, director of the division of signal transduction at BIDMC and professor of systems biology at HMS, in whose laboratory the PI3K pathway was first discovered. "This new discovery suggests that tumors that result from activation of the PI3K/AKT pathway are unlikely to be metastatic unless another mutation occurs to circumvent the block on invasion. The results also suggest that the status of the NFAT pathway that is implicated in invasion should be evaluated in breast tumors."

The study also points out the extremely complex nature of cancer cell pathways.

"We now know that AKT has very different - even competing - functions in its dual roles as both a survival kinase and a motility kinase," says Toker. "In terms of developing future therapies, this poses a host of new questions and challenges and above all, indicates that much more work is needed to arrive at a comprehensive picture of the role of AKT in cancer before it can be targeted for therapeutic purposes."

Study coauthors include BIDMC investigators Merav Yoeli-Lerner, PhD, Gary K. Yiu, PhD, and Isaac Rabinovitz, PhD; Peter Erhardt, PhD, of the Boston Biomedical Research Institute; and Sebastien Jauliac, Ph.D., of Hopital Saint-Louis, Paris, France.

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