Drug Research and Development

Biomarkers – Drug Research and Development:


Biomarker has gathered a huge buzz and speculation around its concept, as it seems to be very fresh. But! It is not. It is a concept that has been around us for a long time. Things such as body temperature and blood glucose levels are considered as common biomarkers. It is a substance used as an indicator of a biological state. Biomarkers or biological markers can be defined as a biochemical parameter or aspect of the body, which has the ability to evaluate the growth of disease or the effects of the treatment. They are also referred as DNA/RNA characteristics, which indicate the normal pathogenic and biologic processes, and pharmacological responses for therapeutic and other interventions. Their levels in the blood indicate the presence and extent of disease. For example, cholesterol is a biomarker used to identify risk of heart disease.

Discovery of Biomarker:

As biomarker has the ability to evaluate/measure or predict the growth of disease or the effects of the treatments, based on this concept biomarkers was first discovered by Dr Joseph Gold while dealing with common cancer. While diagnosing colon cancer patient he found a substance, which normally found in fetal tissue and named it carcinoembryonic antigen (CEA). By the end of 1970s, a potential serum test had been developed to treat variety of cancers. Additional biomarkers developed in 1980s were CA 19-9 for colorectal and pancreatic cancer, CA 15-3 for breast cancer and CA-125 for ovarian cancer.

Examples of Biomarkers:

1) Molecular : Cell, DNA, RNA, and Proteins
2) Functional : Imaging and Physiologic

Traditional Biomarkers:

A) Molecular : DNA – p53 Status and Protein – EGFR Expression
B) Functional : PO2*, SF2**, Tpot***, Hgb % apoptotic cells, proliferative indices, % S-phase

Important Facts:

Biomarkers are considered as reliable indicators of early diseases. These biomarkers are present in the basal levels in normal individual and higher only when there is a considerable amount of cancer present. Biomarkers are not specific for a single cancer. For examples, patients suffering from Lungs or Breast Cancer may have elevated CAE, and CA-125 can be high in women with noncancerous gynecological conditions.

PSA (Prostate Specific Antigen) is the well-known cancer biomarker to detect diseases at its earlier stage. PSA is measured in nanograms or millimeters of blood. Normally men have below 4 nanograms, and anything above 4 indicates prostate cancer.

What is a normal level of PSA?

As per the American Cancer Society, a PSA level between 4 and 10 indicates 25% chance of it being prostate cancer. A PSA higher than 10, increases the chance of having prostate cancer to 50% and above.

Factors that elevate PSA:

  • Ejaculation (no ejaculation at least two days prior to test)
  • Inflammation of the prostate gland
  • Non-cancerous enlargement of the prostate
  • PSA levels can naturally increase with age

Use of Biomarkers:

Biomarkers are useful in predicting outcomes during the course of disease including early detection, outcome prediction, and detection of disease recurrence. With the clinical appearances of many new therapeutic agents, appropriate biomarkers can be used to determine which tumors will respond to which treatments in order to predict the likelihood of drug resistance. Biomarkers are especially useful in the cross-sectional probe of acute disease due to the pharmacologic properties of the chemical or toxin.

Biomarker in pharma industry is for:

  • Preclinical toxicity studies
  • Preclinical stages
  • Clinical development phase

The potential uses of this class of biomarkers include:

  1. Identification of individuals destined to become affected or who are in the “preclinical” stages of the illness.
  2. Reduction in disease heterogeneity in clinical trials or epidemiologic studies.
  3. Reflection of the natural history of disease encompassing the phases of induction, latency and detection.
  4. Target for a clinical trial. The improvement in validity and precision far outweigh the difficulty in obtaining such tissues from patients.

Use of Biomarkers in Cancer:

  1. Widespread screening: Cancer biomarkers are used in widespread screening in order to detect asymptomatic individuals with disease at a very early stage. US FDA has approved PSA and DRE as the tumor biomarker for widespread screening.
  2. PSA Velocity: The change in PSA level over the time is known as PSA velocity. The patient whose PSA level is reported more than 2.0 nanograms during the year prior to diagnosis of prostate cancer, were expected to be at higher risk of dying from the disease.
  3. PSA Density: It is the relationship of PSA level to the size and weight of the prostate. Its value is divided by the prostate size. PSA density is use to interpret PSA results that is controversial because prostate cancer might be overlooked in a man with an enlarged prostate.

FDA approved Biomarkers: Some of the FDA approved Biomarkers are as follows:

  • Bladder Tumor Antigen
  • ImmunoCyt
  • Nuclear Matrix Protein-22
  • Fluorescent In Situ Hybridization
  • Investigational tests such as: Urinary bladder cancer test, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, Survivin, and telomerase).

Future of Biomarkers:

The demand for the development of new treatment has increased the need for biomarkers, which can predict the outcome and also direct as to which treatment options are most likely to be effective for a particular patient with particular tumor. In future biomarkers will play a major role in determining the cost effectiveness in clinical cancer management. For this to be practically possible, it requires simple, inexpensive, reliable, and robust method. Altogether biomarker is an important constituent of the human body and has fascinated many researchers and scientists around the world.

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