A while back I wrote about how circulating tumour cells (CTC’s) see here and here, can be used as a potential new surrogate measure for prostate cancer, so it was with great interest that I read an excellent article (free public link courtesy of AACR) on abnormal circulating cells in non-small cell lung cancer (NSCLC) late last week.
Essentially, this new research from three academic institutions (MD Anderson TX, Manchester UK and Baltimore, MD) set out to:
“Determine if a fluorescence in situ hybridization (FISH)–based assay using isolated peripheral blood mononuclear cells (PBMCs) with DNA probes targeting specific sites on chromosomes known to have abnormalities in non–small cell lung cancer (NSCLC) cases could detect circulating genetically abnormal cells (CACs).”
In the recent discussion about fluid-based blood biomarkers, we saw how people could be spared invasive and inconvenient tumour biopsies, which are not always practical in advanced lung cancer, particularly if the patient is elderly or frail. In this study, the researchers demonstrated that detection of circulating epithelial cells (CECs) or CTCs using a simple blood test may assist in early detection of lung cancer at diagnosis and relapse and provide a minimally invasive way to monitor results of therapy.
Now in this study, only a small number of people with NSCLC were evaluated (NSCLC n=59 plus n=29 controls), but they do give us an indication of what could be looked at in larger scale clinical trials (first find your needle in the haystack!) The presence or increased numbers of these circulating abnormal cells confers a poorer prognosis, ie associated with relapse of disease and poorer survival, so the ability to pick them up earlier and more easily would be an advantage clinically.
The approach used in this research was a commonly used technique called fluorescence in situ hybridization (FISH) to detect abnormal circulating cells that have aberrations found in non-small cell lung cancer. FISH detects and quantifies abnormal cells by using dye-labeled DNA probes of cell chromosomes that cause cells with the targeted genetic abnormalities to light up when viewed under a fluorescent microscope.
The researchers chose 12 biomarker probes that target aberrations previously connected to lung cancer to analyze both the controls (people without lung cancer) and people with NSCLC, including both smokers and non-smokers. In the analysis they found the following:
- Highly significant differences in the average number of abnormal cells in the bloodstream between patients and controls.
- Abnormal cells were significantly associated with disease stage, with cells that contained certain abnormalities increasing significantly as cancer progressed from early to advanced stage disease.
- Eight of the biomarkers had a strong overall correlation between abnormal circulating cells and tumors. Chromosomal gain of the EGFR gene in circulating cells was significantly associated with the same gain in tumors, particularly in patients with stage III or stage IV disease.
No doubt work will soon be underway to develop a commercial clinical test based on FISH, which would then be able to be used in the Community Oncology setting, where the majority of patients are treated in the US. Validation in clinical trials will be crucial to this process.
In an MD Anderson news release, the lead author, Ruth Katz, was quoted as saying:
“Blood tests for these circulating tumor cells could be used to diagnose lung cancer earlier, monitor response to therapy and detect residual disease in patients after treatment.”
Source: MD Anderson Cancer Center
Having an easier to use test to monitor responses more accurately to products in development will be particularly useful for pipeline drugs.
Katz, R., He, W., Khanna, A., Fernandez, R., Zaidi, T., Krebs, M., Caraway, N., Zhang, H., Jiang, F., Spitz, M., Blowers, D., Jimenez, C., Mehran, R., Swisher, S., Roth, J., Morris, J., Etzel, C., & El-Zein, R. (2010). Genetically Abnormal Circulating Cells in Lung Cancer Patients: An Antigen-Independent Fluorescence In situ Hybridization-Based Case-Control Study Clinical Cancer Research, 16 (15), 3976-3987 DOI: 10.1158/1078-0432.CCR-09-3358