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Tumor cells seek temporary shelter from cancer drugs
Date:4/1/2010

mensional structure (known as chromatin). That altered chromatin state depends on a particular enzyme that chemically modifies the histone proteins that are often likened to spools for DNA.

The new results add to other recent work suggesting that drug resistance might not always have to arise through genetic mutation, Settleman said. For example, accumulating evidence suggests that a small population of "cancer stem cells" is intrinsically more difficult to treat.

A handful of other studies have also raised the possibility that epigenetic mechanisms like the one now described might be at play, the researchers note. This path to reversible drug resistance may explain an increasingly observed phenomenon in cancer therapy -- the so-called "re-treatment response" in which cancer patients who have grown resistant to a variety of anticancer drugs can be successfully re-treated with the same drug after a "drug holiday."

The new study also suggests a promising new kind of combination cancer therapy designed to avoid drug resistance or as secondary treatment for cancers that have already developed resistance to other drugs. Indeed, the researchers found that their drug-tolerant cells in culture could be killed by treating them with IGF-1 receptor blockers or chromatin-modifying agents. "It presents a therapeutic opportunity," Classon said.

In fact, the researchers say they've already launched a clinical trial in patients with lung cancer to test a combination therapy including a chromatin-modifying agent and the drug erlotinib, which is a tyrosine kinase inhibitor.

"Although the trial is not yet completed, the early clinical data indicate that the inclusion of a chromatin-modifying agent can dramatically improve clinical benefit in a subset of patients demonstrating acquired tyrosine kinase inhibitor resistance," the researchers wrote in conclusion. "When considering that acquired drug resistance may involve multiple distinct molecula
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Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

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