The term biomarker, or biological marker, refers to a broad range of measures which capture what is happening in a cell or organism at a given moment. Biomarkers are objective medical signs (as opposed to symptoms reported by the patient) used to measure the presence or progress of disease, or the effects of treatment. Biomarkers can have molecular, histologic, radiographic, or physiological characteristics. Examples of biomarkers include everything from blood pressure and heart rate to basic metabolic studies and x-ray findings to complex histologic and genetic tests of blood and other tissues. Biomarkers are measurable and do not define how a person feels or functions. 
 
Although the term biomarker is relatively new, medical signs have been used in clinical practice for centuries.  Many biomarkers, such as heart rate, urinalysis and blood lead levels, are commonly used and well-researched. With the rise of genomics and other advances in molecular biology, new biomarker studies have entered a promising era with potential for early diagnosis and effective, personalized treatment of many diseases. In clinical trials, biomarkers can serve as intermediate markers of a disease and help determine if a specific therapy is effectively treating that disease. The more conventional approach of using endpoints like quality of life or mortality in clinical studies can make accruing enough data both time and cost prohibitive. Using a biomarker-driven approach may shorten clinical trial time and speed up product development and regulatory approval. 

Types of Biomarkers

Types of biomarkers include the following:

1. Molecular – have biophysical properties, which allow their measurements in biological samples (eg, plasma, serum, cerebrospinal fluid, bronchoalveolar lavage, biopsy)
2. Radiographic – obtained from imaging studies
3. Histologic – reflect biochemical or molecular alteration in cells, tissues or fluids
4. Physiologic – measures of body processes

Examples:

• Blood glucose (molecular)
• Grading and staging of cancers (histologic)
• Bone mineral density (radiographic)
• Blood pressure (physiologic) 

Applications of Biomarkers

Biomarkers have many useful applications in health care, including disease prevention and detection, determination of individual disease risk, and disease monitoring. They can also be used to measure the safety or toxicity of a therapeutic regimen or certain environmental exposures.
 

Applications of Biomarkers
Biomarker Application	Biomarker Examples	Disease state
Screening	Prostate specific antigen (PSA)	Prostate cancer
	Fecal occult blood test	Colon cancer
Susceptibility/Risk	Breast cancer genes 1 and 2 mutations (BRCA 1/2)	Predisposition to developing breast cancer
	Factor V Leiden	Predisposition to developing thromboembolism
	Apolipoprotein C	Predisposition to developing Alzheimer’s disease
	Human papillomavirus (HPV)	Predisposition to developing cervical cancer
Diagnostic	Troponin-I	Coronary ischemia
	Sweat chloride	Cystic fibrosis
	Ejection fraction (EF)	Cardiomyopathy/congestive heart failure
	Glomerular filtration rate (GFR)	Chronic kidney disease
Prognostic	BRCA 1/2	Likelihood of second cancer in women with breast cancer
	Chromosome 17p deletions and TP53 mutations	Likelihood of death in patients with chronic lymphocytic leukemia
Monitoring	Serum low-density lipoprotein (LDL)	Response to lipid lowering drugs
	International Normalized Ratio (INR)	Efficacy of anticoagulant therapy
	Cancer antigen 125 (CA-125)	Ovarian cancer disease status or burden
	Hemoglobin A1C	Response to antihyperglycemic agents or lifestyle changes
	Viral load	Response to antiretroviral treatment for human immunodeficiency virus (HIV)
Safety	Hepatic aminotransferases and Bilirubin	Hepatotoxicity
	Serum creatinine	Nephrotoxicity
	Serum potassium	Hypo or Hyperkalemia while taking diuretics, angiotensin converting enzyme inhibitors
	Corrected QT interval (QTc)	Assess potential for drugs to induce ventricular tachycardia
	Serum Bisphenol A (BPA)	Measured in pregnant women; predicts adverse birth outcomes such as preterm birth; has informed/improved public safety through BPA-free plastics.

The use of validated biomarkers in basic and clinical research as well as in clinical practice has become commonplace, and their presence as endpoints in clinical trials is now broadly accepted. Biomarkers allow for better understanding disease processes and the ways in which drugs work to combat disease. This knowledge can be used to diagnose disease earlier, or to prevent it before it starts. Biomarkers can be used to improve the efficacy and safety of existing medicines and to develop new medicines. New molecular biomarkers have the potential to personalize disease prevention and management, making the delivery of healthcare more precise, safe and cost effective, ultimately improving health outcomes.

References:
Amur, S. (n.d.) Biomarker terminology:  Speaking the same language. U.S. Food and Drug Administration online educational materials retrieved from https://www.fda.gov/files/BIOMARKER-TERMINOLOGY--SPEAKING-THE-SAME-LANGUAGE.pdf

BEST (Biomarkers, EndpointS, and other Tools) Resource. May 2, 2018.  FDA-NIH Biomarker Working Group. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK326791/pdf/Bookshelf_NBK326791.pdf

Lou, E., Johnson M., Sima, C., Gonzalez-Espinoza, R., Fleisher, M., Kris, M., & Azzoli, C., (2014). Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer. Cancer Biomarkers, 14(4). doi: 10.3233/CBM-140399

Strimbu, K. & Tavel, J. (2010). What are biomarkers? Current Opinion in HIV and AIDS, 5(6). doi: 10.1097/COH.0b013e32833ed177

World Health Organization (2001). International Programme on Chemical Safety Biomarkers in Risk Assessment: Validity and Validation. Retrieved from http://www.inchem.org/documents/ehc/ehc/ehc222.htm.  Accessed November 9, 2019. 

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