University of Colorado Cancer Center test helps reduce risk of death in advanced lung cancer

Researchers at the University of Colorado Cancer Center have developed a test that identifies key biomarkers in advanced lung cancer that helped reduce the risk of death by 36 percent over a 30- month period in a recent clinical trial.

"We are moving from a one-size-fits-all model to more personalized medicine in lung cancer," said University of Colorado School of Medicine Professor Fred R. Hirsch, MD, Ph.D., a Cancer Center investigator who developed the test along with colleague Wilbur Franklin, MD. "This is a completely new paradigm in treating cancer."

The test was developed in 2003 when Hirsch and his colleagues created a scoring system ranging from 0 to 400 that identified patients with the highest levels of the protein Epidermal Growth Factor Receptor (EGFR). Those scoring over 200 had a better prognosis.

A clinical trial held in Europe known as the FLEX-study, found that 30 percent of the advanced lung cancer patients who took part had high levels of the EGFR protein identified by the University of Colorado Cancer Center test.

The trial consisted of 1,125 advanced lung cancer patients separated into two groups. One group received standard chemotherapy while the other had chemotherapy along with the drug cetuximab, an antibody that attaches to EGFR receptors atop lung cancer cells and often inhibits their growth.

Lung Cancer Biomarkers Given the many different genetic and epigenetic changes involved in malignant transformation in lung cancer, it is clear that there are innumerable potential biomarkers. With progress in understanding the biology of lung carcinogenesis, the development of high-throughput techniques for biomarker discovery and increased focus on early detection of lung cancer, the field of lung cancer biomarkers has undergone a minor explosion. No biomarker has yet been shown to have adequate sensitivity, specificity and reproducibility to be validated as a biomarker for the early detection of lung cancer. We provide an overview of some promising recent studies of lung cancer biomarkers.

Circulating DNA

Levels of circulating cell-free DNA in plasma and serum are generally reported to be higher in patients with cancer than in healthy controls.

Genetic Changes

Since loss of genetic material from chromosome 3p is one of the earliest genetic changes occurring during bronchial carcinogenesis, several studies have looked at whether these changes - microsatellite instability and loss of heterozygosity - could be found in circulating DNA.

Gene Hypermethylation

Methylation of promoters in multiple different tumor suppressor genes occurs early in the development of lung cancer. Hypermethylation of gene promoter regions is associated with silencing of transcription. Silencing by hypermethylation affects genes involved in all aspects of normal cell function, and is a critical trigger for malignant transformation and progression. Methylation can be detected by methylation-specific polymerase chain reaction analysis. In the methylation-specific polymerase chain reaction, bisulfite is used to convert all unmethylated (but not methylated) cytosines to uracil, and then amplification is performed with primers specific for methylated versus unmethylated DNA.