Impaired gene helps non-small cell lung cancer resist drug

HOUSTON - Lung cancer cells with a defective version of a potential tumor suppressor gene are highly resistant to attack by a platinum-based drug commonly used to treat the disease, researchers at The University of Texas M. D. Anderson Cancer Center and The University of Texas Southwestern Medical Center at Dallas report in the cover article of the Oct. 1 edition of Cancer Research.

The gene may provide a potential biomarker for selecting among chemotherapy choices for non-small-cell lung cancer as well as a therapeutic target for restoring the drug cisplatin's punch in treating resistant forms of the disease, says senior author Lin Ji, Ph.D., associate professor in M. D. Anderson's Department of Thoracic and Cardiovascular Surgery.

Researchers at the two institutions, working under a joint National Cancer Institute Specialized Program of Research Excellence (SPORE) in Lung Cancer grant, have identified three tumor-suppressor genes on chromosome 3. The latest paper refines the impact of one of those genes, NPRL2, on the most common form of lung cancer.

"NPRL2 has potential predictive value for care," Ji said. "If a patient's non-small-cell lung cancer lacks an active NPRL2 gene, then cisplatin likely would not be a suitable chemotherapy."

Researchers started by analyzing NPRL2 expression in 40 different lines of non-small-cell lung cancer. They found that 21 lines expressed the gene and of those 15 lines were sensitive to cisplatin. The other 19 lines had little or no expression of NPRL2 and 15 of those were cisplatin-resistant.

Follow-up laboratory experiments with resistant cell lines showed that NPRL2 expression with cisplatin drastically limited cancer cell proliferation and increased programmed cell death (apoptosis) of cancer cells by 2 to 3 fold.

"We also demonstrated in a mouse model of human cisplatin-resistant non-small-cell lung cancer that gene therapy to restore NPRL2's function makes the tumors o

Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center

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