Biomarker (medicine)

In medicine, a biomarker is a measurable indicator of the severity or presence of some disease state. More generally a biomarker is anything that can be used as an indicator of a particular disease state or some other physiological state of an organism. In medicine, a biomarker is a measurable indicator of the severity or presence of some disease state. More generally a biomarker is anything that can be used as an indicator of a particular disease state or some other physiological state of an organism. A biomarker can be a substance that is introduced into an organism as a means to examine organ function or other aspects of health. For example, rubidium chloride is used in isotopic labeling to evaluate perfusion of heart muscle. It can also be a substance whose detection indicates a particular disease state, for example, the presence of an antibody may indicate an infection. More specifically, a biomarker indicates a change in expression or state of a protein that correlates with the risk or progression of a disease, or with the susceptibility of the disease to a given treatment. Biomarkers can be characteristic biological properties or molecules that can be detected and measured in parts of the body like the blood or tissue. They may indicate either normal or diseased processes in the body. Biomarkers can be specific cells, molecules, or genes, gene products, enzymes, or hormones. Complex organ functions or general characteristic changes in biological structures can also serve as biomarkers. Although the term biomarker is relatively new, biomarkers have been used in pre-clinical research and clinical diagnosis for a considerable time. For example, body temperature is a well-known biomarker for fever. Blood pressure is used to determine the risk of stroke. It is also widely known that cholesterol values are a biomarker and risk indicator for coronary and vascular disease, and that C-reactive protein (CRP) is a marker for inflammation. Biomarkers are useful in a number of ways, including measuring the progress of disease, evaluating the most effective therapeutic regimes for a particular cancer type, and establishing long-term susceptibility to cancer or its recurrence. The parameter can be chemical, physical or biological. In molecular terms biomarker is 'the subset of markers that might be discovered using genomics, proteomics technologies or imaging technologies. Biomarkers play major roles in medicinal biology. Biomarkers help in early diagnosis, disease prevention, drug target identification, drug response etc. Several biomarkers have been identified for many diseases such as serum LDL for cholesterol, blood pressure, and P53 gene and MMPs as tumor markers for cancer. It is necessary to distinguish between disease-related and drug-related biomarkers. Disease-related biomarkers give an indication of the probable effect of treatment on patient (risk indicator or predictive biomarkers), if a disease already exists (diagnostic biomarker), or how such a disease may develop in an individual case regardless of the type of treatment (prognostic biomarker). Predictive biomarkers help to assess the most likely response to a particular treatment type, while prognostic markers shows the progression of disease with or without treatment. In contrast, drug-related biomarkers indicate whether a drug will be effective in a specific patient and how the patient’s body will process it. In addition to long-known parameters, such as those included and objectively measured in a blood count, there are numerous novel biomarkers used in the various medical specialties. Currently, intensive work is taking place on the discovery and development of innovative and more effective biomarkers. These 'new' biomarkers have become the basis for preventive medicine, meaning medicine that recognises diseases or the risk of disease early, and takes specific countermeasures to prevent the development of disease. Biomarkers are also seen as the key to personalised medicine, treatments individually tailored to specific patients for highly efficient intervention in disease processes. Often, such biomarkers indicate changes in metabolic processes. The 'classic' biomarker in medicine is a laboratory parameter that the doctor can use to help make decisions in making a diagnosis and selecting a course of treatment. For example, the detection of certain autoantibodies in patient blood is a reliable biomarker for autoimmune disease, and the detection of rheumatoid factors has been an important diagnostic marker for rheumatoid arthritis (RA) for over 50 years.For the diagnosis of this autoimmune disease the antibodies against the bodies own citrullinated proteins are of particular value. These ACPAs, (ACPA stands for Anti-citrullinated protein/peptide antibody) can be detected in the blood before the first symptoms of RA appear. They are thus highly valuable biomarkers for the early diagnosis of this autoimmune disease. In addition, they indicate if the disease threatens to be severe with serious damage to the bones and joints, which is an important tool for the doctor when providing a diagnosis and developing a treatment plan. There are also more and more indications that ACPAs can be very useful in monitoring the success of treatment for RA. This would make possible the accurate use of modern treatments with biologicals. Physicians hope to soon be able to individually tailor rheumatoid arthritis treatments for each patient. According to Häupl T. et al. prediction of response to treatment will become the most important aim of biomarker research in medicine. With the growing number of new biological agents, there is increasing pressure to identify molecular parameters such as ACPAs that will not only guide the therapeutic decision but also help to define the most important targets for which new biological agents should be tested in clinical studies. An NIH study group committed to the following definition in 1998: 'a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.' In the past, biomarkers were primarily physiological indicators such as blood pressure or heart rate. More recently, biomarker is becoming a synonym for molecular biomarker, such as elevated prostate specific antigen as a molecular biomarker for prostate cancer, or using enzyme assays as liver function tests. There has recently been heightened interest in the relevance of biomarkers in oncology, including the role of KRAS in colorectal cancer and other EGFR-associated cancers. In patients whose tumors express the mutated KRAS gene, the KRAS protein, which forms part of the EGFR signaling pathway, is always ‘turned on’. This overactive EGFR signaling means that signaling continues downstream – even when the upstream signaling is blocked by an EGFR inhibitor, such as cetuximab (Erbitux) – and results in continued cancer cell growth and proliferation. Testing a tumor for its KRAS status (wild-type vs. mutant) helps to identify those patients who will benefit most from treatment with cetuximab.