Point-of-care biosensor systems for cancer diagnostics/prognostics
Introduction
Cancers arise as a result of the disruption of normal cell signaling pathways, which can produce cells (cancer cells) that exhibit a decisive growth advantage compared to their neighbors. These growth advantages are typically produced from a number of different genetic and/or epigenetic changes, which result in the activation of oncogenes and the inactivation of tumor suppressor genes. Unfortunately in terms of diagnosis, no single oncogene or tumor suppressor gene has been discovered to be universally altered in all adult cancers. In addition, patterns of genetic and/or epigenetic changes differ not only in terms of tumor location (i.e., organ), but also among tumors from the same location. Besides genome-related changes, other complex molecular alterations result during the course of tumorigenesis, such as gene over/under-expression (mRNA changes) or protein over/under-expression. As such, a plethora of molecular biomarkers can potentially be analyzed via different sensing platforms for tumor classification to guide diagnosis, prognosis, monitoring treatment and disease recurrence.
As depicted in Fig. 1, the age-adjusted death rate for heart disease has dramatically declined over the last 50 years, while in the case of cancer this same trend has not occurred (Leaf, 2004). In 2004, nearly 563,700 patients were diagnosed with one or several of the 100 diseases belonging to the cancer family with one in two and one in three men and women, respectively, expected to contract one of these diseases during their lifetime. It is interesting to note that ∼90% of all cancer-related deaths occur from metastasis and not directly from the primary tumor site.
In spite of the rapid explosion of new technology platforms and biomarkers that have been discovered and reported in the literature for cancer diagnostics, prognostics, therapeutics and monitoring disease recurrence, few of these technologies or biomarkers have transitioned into the clinical arena. The common method for cancer diagnosis and prognosis relies heavily on technologies that are over 100 years old (paraffin fixation of tissues with visual inspection of cell morphology by a pathologist). Therefore, in spite of the significant investment by a number of agencies into discovery of new molecular markers and the technologies to utilize these biomarkers, most have not entered the clinic. The major fundamental question then arises: Why have the incidence and survival rates of cancers not shown marked decreases in line with the large financial and time investments that have been waged against this disease? In this paper, information will be presented that provides information on potentially new technologies in the form of point-of-care (POC) biosensors for biomarker analysis and the merging of new biomarkers with the appropriate technology platform to develop systems that provide clinically relevant information to assist the physician and clinician in disease diagnosis, prognosis, treatment and recurrence. The major technology platform that will be the focus of this discussion is biosensors, and their integration into POC systems for the analysis of clinically significant cancer biomarkers.
Section snippets
Description of technology area
A biosensor (see Fig. 2) in the traditional sense is defined as: bioanalytical device incorporating a biological material or a biomimic (e.g., tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, etc.), intimately associated with or integrated within a physicochemical transducer or transducing microsystem, which may be optical, electrochemical, thermometric, piezoelectric or magnetic. The usual aim of a biosensor is to produce either discrete or continuous
Novel technologies for POC biosensing platforms for cancer diagnostics
POC technologies offer platforms for complex testing by non-specialists and the benefit of increased robustness and reliability due to fewer world-to-device interfaces. These technologies can contribute to the realization of personalized medicine by creating a link between the diagnosis of disease and the ability to tailor therapeutics to the individual. As biomarkers of disease are discovered and validated through genomics and proteomics research, development of new technology platforms can
Summary and conclusions
Extensive work within the physical sciences and engineering fields has resulted in the evolution of a variety of new tools that are well-equipped to monitor the presence or absence of certain biomarkers across a number of different classes (DNA, RNA and proteins). Indeed, many of these devices have already been employed in the clinic for the diagnosis and/or prognosis of certain diseases. However, the use of these sensing platforms for cancer has been slow to evolve due primarily to the
Future perspectives and technology needs for meeting the demands of cancer diagnosis/prognosis
While much research has evolved as a result of opportunities from a variety of agencies, including the NIH, it is clear that new technology-focused funding opportunities will have to be developed to produce a new wave of biosensors that are appropriate for providing clinically relevant information for the 100 or so cancer-related diseases. During the evolution of biosensor related platforms for providing clinical information for cancer patients, the following issues should be kept under
FDA and the regulation of in vitro diagnostic devices (IVDs)
The efficient translation of new technologies into clinical use is benefited by the early involvement of the FDA. FDA began regulating medical devices, including IVDs or laboratory tests, with the passage of the Medical Device Amendments of 1976. This new law put into place a series of general controls for medical devices including the requirement that companies register and list their products with FDA, make these products consistently over time following good manufacturing practices, and
Acknowledgements
The authors would like to thank the National Institutes of Health (National Cancer Institute) for supporting the workshop (June 2005, Bethesda, MD) from which this document evolved.
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