New Clues to Lung Cancer Drug Resistance

[dadstimeon]

http://www.ajc.com/health/content/share ... 24094.html

[Hebbie]

I found a similar article on this subject:

Second mutation in EGFR gene linked to acquired resistance to gefitinib

contrast, no evidence of the T790M mutation was found in untreated tumor specimens. The authors also found that this mutatio

Reuters Health

Posting Date: February 22, 2005

Last Updated: 2005-02-22 9:44:12 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Gain of functional mutations in the gene for epidermal growth factor receptor (EGFR) renders lung adenocarcinomas sensitive to gefitinib (Iressa) and erlotinib (Tarceva), but it appears that a second mutation in this gene results in acquired resistance to these agents.

The findings, which appear in the February 22nd issue of Public Library of Science (PLoS) Medicine, are based on a genetic analysis performed in five patients with acquired resistance to gefitinib or erlotinib.

In addition to the primary sensitizing EGFR mutation, two of the patients had a mutation in exon 20 of the gene, lead author Dr. William Pao, from the Memorial Sloan-Kettering Cancer Center in New York, and colleagues note.

This second mutation, known as T790M, was located in the kinase domain of EGFR and involved the substitution of methionine for threonine. Testing in a sixth patient with disease which later became resistant to gefitinib also demonstrated the presence of this mutation.

In vitro testing showed that the T790M mutation made cancer cells with sensitizing EGFR mutations resistant to gefitinib and erlotinib. A mutation similar to T790M that affects other kinases has been associated with acquired resistance to imatinib (Gleevec), the researchers point out.

"We are now trying to figure out other possible reasons why gefitinib or erlotinib stop working," Dr. Pao said in a statement. "We also hope to identify mutations in other potential cancer-causing genes that are critical for lung cancers to survive."

PLoS Medicine 2005;2.

[tnmynatt]

Is there a way to get the Tarceva and Iressa club folks tested for this mutation? Any ideas? What about the experts? You think they could help us with this or do we want to know?