Biomarkers are defined in broadly different terms. However, an often-quoted definition describes them as
        a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention (Biomarkers Definitions Working Group 2001: 91).  
      Biomarkers come in different forms and shapes. In a nutshell, we can differentiate biomarkers according to their predominant area of application:
       [1] Biomarkers enrolled in diagnostics, where they are involved in categorizing individuals into groups that are          included in or excluded from the bio-medical system;
       [2] Biomarkers applied in therepeutics, where they help decisions on how to treat individuals once they are          included into the bio-medical system; and
       [3] Biomarkers in drug development.
      In the categorization of (mostly asymptomatic) individuals, biomarkers come in two forms:
    as “risk markers” and
    as “diagnostic markers”.
      “Risk markers” involve the detection of mutations or variants in the germline DNA or an individual. Such mutations might involve entire genes or polymorphisms in a gene or a non-coding region of a genome. With the exception of rare monogenetic diseases that are caused by mutated genes, risk markers do not predict future diseases but aid in calculating the risks of individuals to contract specific conditions in the future. Individuals proven to be carriers of such DNA variants are then encouraged to take preventive actions, ranging from taking drugs (if available) or undergoing preventive therapies to undertaking diet or life-style changes, and/or are entitled to be included in screening or surveillance programs to detect eventual diseases at an early stage of disease progression. A well-known example of such a risk marker involves the BRCA-1 and BRCA-2 genes, which are involved in familial breast cancer. Several mutations of these genes are known to confer a substantially higher risk of breast cancer and a higher risk of ovarian cancer in women with mutations in this gene.
      Beside risk markers, “diagnostic markers” indicate the presence of a particular disease in an individual or patient, thereby facilitating the categorization of individuals into groups of patients who are candidates for more invasive diagnostic practices and eventually treatments. Such diagnostic markers can also be used as “screening markers” for asymptomatic populations or as “monitoring markers” to monitor conditions. Similar to “risk markers”, which allow not statements about actual futures but estimates about possible ones, diagnostic markers are not in themselves classified as diseases. Rather, they function as indicators that a condition might be present in an individual’s body. The practice of measuring levels of prostate-specific antigen (PSA), a protein produced by the cells of the prostate gland, is an example for such a diagnostic marker. PSA levels have been found to be increased in the blood of individuals having prostate cancer. Since the early 1990s, PSA-based tests have been used to detect males suffering from asymptomatic prostate cancer at an early stage of cancer development. Individuals with elevated PSA levels are further examined through more invasive diagnostic procedures, such as digital rectal examination or ultrasound, and are eventually referred for biopsies.
[2] Biomarkers in therapeutics
      Another important area in which biomarkers are deployed in the present, and in which current research efforts try to increase their number, is therapeutics. Here biomarkers are used to individualize therapies, tailoring therapies to subgroups of patients or targeting treatments to subtypes of diseases. Such “theragnostic markers” help clinicians to decide which patients to treat and to choose the therapy most likely to be effective for a given patient. They come primarily in two forms:
    as prognostic markers and
    as predictive markers.
      “Prognostic biomarkers” aid the prediction of the clinical outcome for a patient if no therapy is administered. Hence, they allow judgments on whether or not more aggressive treatments are reasonable for some patients. While prognostic biomarkers allow judgments on whom to treat, “predictive markers” facilitate decisions on how to treat a patient. An example for such a prognostic marker relates the breast-cancer drug Herceptin (the brand name for Trastuzumab). This monoclonal antibody targets patients with breast tumors that have an increased copy number of the gene HER2 (also known as ERBB2 or NEU). Hence, in order to decide whether or not to treat a patient with Herceptin, health care workers test the tumor for an excess of HER2 protein or for a copy number amplification of the gene that encodes this protein.
[3] Biomarkers in Drug Development
      Biomarkers are also salient in the field of drug development, in which they are imagined as helpful devices to smooth the drug development process and to streamline the translation of drug candidates. Here biomarkers are expected to aid the identification of novel pathways and drug targets, marking key molecule involved in a pathway that is specific to a condition. Furthermore, biomarkers can be used to aid the stratification of patients in order to select patients who are likely to be more responsive to the trial pharmaceutical, and as “surrogate endpoints”, substituting clinical outcomes. These can often be measured years before meaningful clinical endpoints such as mortality occur.
Updated 24.04.2010