The failure of discoveries involving cancer biomarkers to fuel clinical success may stem from many problems, according to a study published in the Journal of the National Cancer Institute (2010 Aug 12. [Epub ahead of print]).
According to the press release announcing the findings, the National Institutes of Health defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”
The study, led by Eleftherios Diamandis, MD, PhD, professor of pathology and laboratory medicine at Mount Sinai Hospital in Toronto and associate scientist at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, examined some biomarkers initially hailed as “breakthroughs” and their subsequent failings. The biomarkers included nuclear magnetic resonance of serum for cancer diagnosis; lysophosphatidic acid for ovarian cancer; four- and six-parameter diagnostic panels for ovarian cancer; osteopontin for ovarian cancer; early prostate cancer antigen-2 (EPCA-2) for prostate cancer detection; proteomic profiling of serum by mass spectrometry for ovarian cancer diagnosis; and peptidomic patterns for cancer diagnosis.
Dr. Diamandis reported that the reasons for biomarker failures ranged from inappropriate statistical analysis to biases in case patient and control subject selection. In one case, Dr. Diamandis pointed out that the problems with EPCA-2 included reporting values that were beyond the detection limit of the assay and using inappropriate reagents to test EPCA-2, such as solid surfaces coated with undiluted serum.
“Problems with pre-analytical, analytical, and post-analytical study design could lead to the generation of data that could be highly misleading,” Dr. Diamandis concluded.