Molecular Pathway Predicts Chemotherapy Effectiveness for Lung Cancer

A common molecular pathway could help physicians predict which lung cancer patients will benefit from chemotherapy drugs.

A fundamental molecule known as the retinoblastoma (RB) tumor-suppressor regulates cell proliferation in the body. The RB pathway is either entirely inactive or altered in most human cancers. Scientists are beginning to use its actions as a "biomarker” for how tumors will respond to different therapies.

Michael Reed, M.D. and colleagues at the University of Cincinnati (UC; Cincinnati, OH, USA) found that turning off the RB pathway in lung cancer cells resulted in an altered response to chemotherapy agents and more cancer cell death. Their findings were reported in the September 2007 issue of the journal Cancer Research.

"Dissecting the RB pathway will help us better understand how chemotherapy works and predict which patients might benefit from therapy and which ones won't,” explained Prof. Reed, assistant professor of surgery at UC and a thoracic surgeon at the University Hospital. "As pathways are further defined, we could choose agents that are targeted to an individual tumor's molecular characteristic.”

For the study, Prof. Reed's team shut off the RB pathway in human non-small cell lung cancer cells and exposed them to chemotherapy agents currently used to treat lung cancer patients. The results showed that when RB was turned off, the cancer cells continued to divide, but became more susceptible to the drugs.

"But the minute you take away the chemotherapy, the cells take off again,” said Prof. Reed. "This suggests that it's not just loss of RB that affects therapy response--it could be changes at various steps in cellular signaling that result in different outcomes. The traditional way of thinking of cancer--one cancer gene to treat and you're done--is obviously not the best approach to treating this disease. These are complex, overlapping molecular pathways. Dissecting them and determining how to use that information to apply combinations of chemotherapeutic agents will allow for individualization of therapy.”

Prof. Reed and his colleagues intend to begin testing the RB tumor-suppressor in human tumor tissue samples from the UC Thoracic Tumor Registry and compare them to patients with known outcomes.


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