The National Institutes of Health (NIH) has awarded $1.5 million to Ite Laird-Offringa, associate professor of surgery, biochemistry and molecular biology at the Keck School of Medicine, and her co-investigators, to search for molecular markers of early lung cancer.
The five-year grant, “Development of DNA Methylation Markers for Early Detection of Lung Cancer,” will “allow us to pursue research that many scientists here at USC have put a lot of time into over the past 10 years,” said Laird-Offringa.
Colleagues Barbara Gitlitz, Michael Koss, Jeffery Hagen and Wendy Cozen are involved in the search for early lung cancer markers, she said. “It speaks to the collaborative nature of the researchers here at USC. We’re excited about this interdisciplinary project.”
Using tumor material from lung cancer patients, Laird-Offringa and colleagues found DNA methylation markers for several types of non-small cell lung cancer—including adenocarcinoma, a common form of lung cancer that often occurs in nonsmoking women, and squamous cell carcinoma. Together they make up almost three-quarters of all lung cancer cases.
DNA methylation involves chemical modifications that can block gene expression. “DNA methylation turns off genes that stop cells from turning cancerous,” Laird-Offringa said. “And it does so in identifiable patterns, creating profiles that differ and can be compared between tumors.”
A pilot study involving 50 cases each of adenocarcinoma and squamous cell cancer showed “that it is possible to use methylation profiles to discriminate between different types of lung cancer. We found about 15 really promising markers. That’s a big step. We are now finishing our development of large cell lung cancer markers.”
The next step, which will be part of the NIH grant research, is to validate these methylation markers in significant numbers of patients and see if they can be used non-invasively to diagnose lung cancer in its earliest stages.
“It has been reported that methylation can be different among ethnic groups, so the grant allows us to look for an additional 100 each adenocarcinoma, squamous, and large cell cancer patients—25 of the major racial/ethnic groups for each lung cancer type. That way we’ll make sure they work for all ethnicities.”
An early detection test for lung cancer, similar to the PSA test for prostate cancer, could have a major impact. Only a small fraction of lung cancers is diagnosed when the disease is “localized,” Laird-Offringa noted.
“Almost three-fourths of all patients are diagnosed with regional or distant disease, and their five-year survival rate is abysmal. The most efficient way to save the lives of lung cancer patients is the same as for any other type of cancer: diagnose early. And for the leading cause of cancer death in the U.S., that would be highly significant,” she said.
Although spiral CT scanning is a sensitive screening tool, it “detects suspicious lesions in half of all long-terms smokers,” she said. “Only 10 percent of those lesions turn out to be cancer. We need a test that can tell if the patient does indeed have lung cancer, and even better, that would be able to distinguish what type of lung cancer it is and use that to determine treatment.”
Laird-Offringa is hopeful, because they have been able to sensitively detect at least one of their methylation markers in patient blood. “But that’s really just pilot data. In order to know if this will work, we need to examine many methylation markers in the blood of 300 patients. If that is successful, a large prospective study will follow.”
Eventually the markers could be used to create individual molecular profiles that could help determine the likely course of the disease and even the patient’s response to treatment.