Foundations for Effective Cancer Biomarkers

By BioProcessing Inc.

A high priority to a large majority of the Pharmaceutical Industry is to develop and introduce new cancer drugs. An increasing number of potential drug targets particularly to tumor cells continue to be discovered and studied. There are more than four thousand gene and gene product, which are implicated in the biology of cancer. However, despite these large numbers of potential biomarkers only a couple of dozen are currently being used clinically which are FDA/EU approved tests.

Tumor marker antigens have been in clinical use since the 1970's. The carcinoembryonic antigen (CEA) blood test used to monitor colon cancer reoccurrence was first approved by the FDA in 1973. Yet, in the thirty plus years since then there have been only about a dozen of such FDA approved similarly used markers are being used in clinical practice. During the past decade genetic tests, primarily PCR based, have been introduced into clinical diagnostics. Much of the progress has been applied to breast cancer. There are at least four gene set tests, which help physicians assess patient risk for the recurrence of breast cancer in determining the need for chemotherapy in hormone or Estrogen receptor positive, node negative breast cancer patients with small tumors. Another test approved to look for recurrance in breast cancer is for circulating tumor cells (CTC). Finding CTCs in he circulation of a post treatment patient has the additional potential to be able to identify surface markers, which may lead to an appropriate, and specific drug therapy. 

All of these types of markers, proteins (tumor markers) in both tissue and blood, DNA in tissue, and tumor cells in blood are clinically useful cancer biomarkers. However, these markers are effective not only because of the compilation of extensive patient clinical trial data required for FDA approval but as importantly because of standardized, reliable test reagents and methods. Early circulating protein tumor markers measured in blood serum were initially radioimmunoassay (RIA) based methods. Unfortunately these manual assays had coefficient of variations (CV) of 10-30%, were labor intensive and had long incubation times.  With the introductions of automated chemiluminescent immunoassay technologies in the mid 1990s these problems were solved resulting in the reduction of assay CVs to about 5%, reduced labor, and shorter assay times. In addition, reagents, in particular, the antigens were primarily made from cell culture sources, which have lead to more consistent assay raw materials.   Likewise, PCR technologies are automated and and reagents improved as compared to those of a decade ago leading to more reliable and effective results.  Finally an automated system for capturing and accurately identifying CRCs has enabled an obvious and important cancer biomarker tool to now be clinically viable. Prior to this technological improvement twenty years of work with CRCs as biomarkers did not meet clinical diagnostic standards.

Fortunately the technologies for measuring proteins, DNA, and tumor cells are all currently in place and ready for expanded applications. Researchers are in a discovery and applications mode now that requires the reliability and consistency of new reagents for these technologies. In order to meet these clinically demanding standards for these critical assay components manufacturers need to use quality controlled methods and systems. Cancer biomarkers should be manufactured according to GMP and/or ISO 9001 13485 standards. Also, biomarkers are being used more frequently in the design of cancer drug trials. Critical assay components as well as appropriate method technologies need to be employed in order to meet pharmaceutical and diagnostic companies' ultimate goals, which are FDA approvable cancer drugs and diagnostic tests.

Contact details:
Gary Goodrich, President
Bioprocessing, Inc., 1045 Riverside Street, Portland , ME 04103
T: 207-457-0025, W: www.bioprocessingin.com