Significant Advances in Lung Cancer Highlighted at AACR
Orlando, FL—Lung cancer studies made news at the 2011 American Association of Cancer Research annual meeting. Research groups identified potential new therapeutic targets; developed a biomarker panel to detect lung cancer in nonsmokers and, possibly, in early-stage mesothelioma; and outlined the potential to reduce the risk for lung cancer in former smokers.
Biomarkers in the Blood
A panel of biomarkers may soon identify the presence of lung cancer in blood samples.When used in conjunction with spiral computed tomography scans, which are not very specific for lung cancer diagnoses, the assay could help triage patients for further assessment.
The 6-biomarker panel was developed from 4 independent studies in smokers. All stages of lung cancer and histologic cell types were distinguishable in the assay. In the current study, the investigators applied the markers to 600 specimens from a nonsmoking population who developed cancer and a healthy control cohort.
“In recent years, more attention has focused on this never-smoker population of lung cancer cases,” said principal investigator Charlie Birse, PhD, Celera Corporation (which is developing the test). “The proportion of lung cancer cases among never-smokers is projected to increase in the coming years, as smoking prevention and cessation programs are introduced.”
An independent validation study among 40 patients with lung cancer who had never smoked confirmed the utility of the test in all cancer stages and all major histologic cell types. “The markers showed a strong performance in the never-smoker study,” Dr Birse said, “with…a sensitivity of 85% and specificity of 83%.”
The test’s performance suggests it would best be used as a complement to imaging for detecting lung cancer in smokers and nonsmokers, he said.
New Test Detects Asbestos-Related Cancer A novel biomarker test appears very accurate in detecting proteins secreted from tumors caused by exposure to asbestos. The test may therefore be able to identify early-stage malignant mesothelioma, an aggressive pulmonary cancer with increasing incidence. Mesothelioma is usually fatal, because it is typically found in an advanced disease stage.
Harvey I. Pass, MD, of New York University Cancer Institute, and colleagues used the SomaLogic aptamer proteomics platform to examine 170 blood samples from 90 patients diagnosed with mesothelioma and 80 persons exposed to asbestos; they found 19 significant biomarkers for mesothelioma and combined these into the Multiplex SOMAmer Assay, which can measure 1000 proteins simultaneously from a small blood sample.
According to Dr Pass, the platform combines the best qualities of an immunoassay and can find and quantify low-abundance proteins secreted by tumor cells. Data on its clinical benefit are not yet available.
New Therapeutic Target A new gene mutation associated with squamous-cell lung cancer may lead to new targeted treatments for this histologic type of cancer, according to Matthew Meyerson, MD, PhD, of Dana-Farber Cancer Institute, Boston.
Several mutations in lung cancer have led to targeted approaches that are now in clinical trials; however, these are largely in adenocarcinoma. “There are very few known targets for the treatment of squamous-cell lung cancer, and no approved targeted therapies,” Dr Meyerson said at a press briefing at the meeting.
He and his colleagues recently discovered that mutations in the DDR2 gene are present in about 4% of all cases of squamous-cell carcinoma of the lung and are associated with sensitivity to the tyrosine kinase inhibitor dasatinib (Sprycel).
In cell lines harboring the DDR2 mutations, cell growth is inhibited by dasatinib, and animal models with the mutation are also sensitive to dasatinib. In addition, 1 patient with squamous-cell lung cancer and DDR2muta – tions had a radiographic re sponse to dasatinib, Dr Meyerson reported.
These data add to the growing list of targets being identified in lung cancer, for which new targeted agents may prove effective.
Chemoprevention with Oral Iloprost
Oral iloprost (Ventavis), an analog of prostacyclin, showed promise as a chemopreventive agent for lung cancer, according to studies done at the Translational Genomics Research Institute in Phoenix, AZ.
The drug significantly improved endobronchial dysplasia in former smokers, as judged by improvements in the average bronchial histologic score (based on the World Health Organization classification of premalignant lesions) and in the dysplasia index score, reported Paul A. Bunn Jr, MD, Executive Director of the Inter – national Association for the Study of Lung Cancer and Professor of Lung Cancer Research, University of Colorado Cancer Center, Denver.
“About half of all smokers have stopped smoking in the United States, and about half of all cases of lung cancer are in former smokers,” he said. “What can we do for these former smokers?”
Iloprost is currently indicated for the treatment of primary pulmonary hypertension. The hypothesis was that if prostacyclin could be stimulated, or if patients were given a prostacyclin analog such as iloprost, lung cancer might be prevented, Dr Bunn said.
The phase 2 trial involved 152 individuals who were current or former smokers exposed to ≥20 pack-years of cigarettes and who had at least mild cytologic atypia on sputum cytology and no history of cancer. Biopsies were performed on all areas that appeared abnormal on bronchoscopy.
Participants were then randomized to oral iloprost or placebo for 6 months. A second bronchoscopy was conducted, and biopsies of all previously sampled areas were repeated and conducted on new suspicious areas as well.
Within the whole cohort, 74% had at least 1 biopsy showing mild dysplasia or worse on the initial bronchoscopy. Lesions were scored from 1 (normal) to 7 (carcinoma in situ). At baseline, as expected, current smokers had worse bronchial histology than former smokers, who had less atypia in the bronchial epithelium.
Former smokers given iloprost showed a significant improvement in the average of all biopsy scores:
- Average scores improved from 3.3 at baseline to 2.1 at 6 months (–1.2 change)
- Worst biopsy scores improved from 4.6 to 3.1 (–1.5 change)
- Dysplasia index improved from 43% to 19.6% (–23.6% change).
“The histologic improvements in iloprost-treated former smokers were larger in magnitude than the difference between current and former smokers,” Dr Bunn reported.