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Study identifies pathway to enhance usefulness of EGFR inhibitors in lung cancer treatment
Date:6/29/2012

Many lung cancers are driven by mutations in the epidermal growth-factor receptor (EGFR), and so it makes sense that many successful modern treatments block EGFR activity. Unfortunately, cancers inevitably evolve around EGFR inhibition, and patients with lung cancers eventually relapse. A University of Colorado Cancer Center study published today in the journal Cancer Research details a signaling pathway, known as 'the canonical Wnt pathway', that lung cancer cells use to escape from EGFR-targeted therapy and suggests that by disrupting this pathway, we could lengthen the usefulness of existing EGFR inhibition therapies.

"As Billy Crystal as Miracle Max said in The Princess Bride, 'There's a big difference between mostly dead and all dead,' and in lung cancer cells, the Wnt pathway could be that difference," says James DeGregori, PhD, investigator at the CU Cancer Center, co-director of the center's Molecular Oncology Program, and the paper's senior author.

Elaborating on DeGregori's very technical description, Matias Cass-Selves, PhD, postdoc in the DeGregori lab and the paper's first author, explains, "The Wnt pathway is an ancient mechanism across species that helps stem cells differentiate into tissue, and maintains stem cells' ability to stay 'stemmy' to produce subsequent generations of cells that can also continue to produce cells. It also maintains adult lung tissue, and now we've shown that it also maintains cancer cells during targeted therapy."

Imagine a dish filled with millions of lung cancer cells. And imagine the cells' genetic material as a shared book. Cass-Selves systematically deleted paragraphs from cells' books to create a population of cells, each with a unique paragraph deleted. Then he treated all the cells with an EGFR inhibitor. Which cells died? Well, a number of paragraphs were responsible for cell death, "But many of the paragraphs missing from the dead cells were within the Wnt chapter," he says.
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Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

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