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Genes May Help Guide Lung Cancer Care

RNA profile could spot patients in need of aggressive treatment, researchers say

WEDNESDAY, March 15, 2006 (HealthDay News) -- Specific genetic patterns may predict the course of lung cancer, researchers report.

The new patterns could help with the diagnosis, prognosis and, eventually, treatment of the disease as the information gleaned is used in drug development.

"Anything that can give us a clue about survival is important," explained Dr. Norman Edelman, chief medical officer of the American Lung Association. "Like many other things of this kind, we hope it just opens the door to new research."

Lung cancer remains the number one cancer killer in the world. Currently, about half of all people with early, stage-1 lung cancer who undergo surgery will see their cancer spread within five years. The problem is that physicians cannot yet predict who will recover and who will not.

While scientists have untangled some of the genetic intricacies of lung cancer, they are still far from having the full picture.

Enter microRNAs or miRNAs, small pieces of genetic material called ribonucleic acid (RNA) that are thought to control gene expression.

"This is a relatively new class of molecules that regulate cells and may be very much involved in the process of normal cells becoming cancer cells," explained co-senior author Dr. Curtis C. Harris, chief of the Laboratory of Human Carcinogenesis at the U.S. National Cancer Institute.

As reported in the March 13 issue of Cancer Cell, Harris' team compared samples of lung cancer tissue and noncancerous lung tissue from 104 patients. The focus was on adenocarcinomas and squamous cell carcinomas -- non-small cell lung cancers that represent about 85 percent of all lung cancers and are notoriously difficult to treat.

About two-thirds of the tumors were adenocarcinomas, and the remainder squamous cell carcinomas.

"We wanted to see if these miRNAs, which regulate other signaling molecules, might have a different and a unique profile in cancer vs. non-cancer, and whether it relates to clinical disease in terms of prognosis or stage," Harris said.

Microarray analysis was used to detect patterns of miRNA expression in each tumor and normal tissue pair. Ultimately, five miRNAs displayed different expression levels in tumor tissues vs. the normal tissues.

Further study revealed that two miRNAs -- has-mir-155 and has-let-7a-2 -- could predict survival. Specifically, lung cancer patients with high levels of has-mir-155 or low levels of has-let-7a-2 had worse survival outcomes than patients with low has-mir-155 or high has-let-7a-2 expression.

Based on these genetic clues, doctors could identify patients with a worse prognosis who may need more aggressive treatment, the authors stated. "More sensitive and specific tests allow you to differentiate the people who have a better prognosis vs. those who don't. It's the idea of personalized medicine," Harris said.

The findings need to be replicated in other studies before they are used in real-life situations, the researcher said. "This is not ready yet for routine clinical practice," Harris said.

That process has already begun, however. Harris was co-senior author of a paper appearing in the Feb. 14 issue of the Proceedings of the National Academy of Sciences. That study found that miRNAs were also involved in the progress of lung, breast, stomach, prostate, colon and pancreatic cancer.

"What we really hope with genetic profiles is that we will be able to say, 'Aha! This profile says that these are the drugs that work best,'" Edelman said. "It's another good step in working through the genetic variations of lung cancer."

More information

For more on non-small cell lung cancer, visit the American Lung Association.

SOURCES: Curtis C. Harris, M.D., chief, laboratory of human carcinogenesis, National Cancer Institute; Norman Edelman, M.D., chief medical officer, American Lung Association; March 13, 2006, Cancer Cell; Feb. 14, 2006, Proceedings of the National Academy of Sciences
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