Interview

'Biomarkers will provide a dynamic approach'

Biomarkers have become a lifeline for researchers and pharmacos. Sushmi Dey finds out more in conversation with Shrikumar Suryanarayan, President-Research & Development, Biocon.

What are biomarkers and how do they exist in the body?

Biomarkers are substances sometimes found in an increased or decreased amounts in the blood, other body fluids, or tissues and which can be used to indicate the presence, progression or regression of some types of diseases for example diabetes or cancer. They are basically cellular or molecular indicators of exposure, disease, or susceptibility to disease. Biomarkers are important components in the body fluids like saliva, urine or blood which is reasonably easily accessible for diagnostic purposes that can indicate an individual's health status. A biomarker is not a genetic indicator. Genetic testing delivers information regarding an individual's potential for developing a certain disease or condition that cannot be addressed through any type of clinical intervention.

What are the different types of biomarkers?

There are two major types of biomarkers—biomarkers of exposure used in risk prediction; and biomarkers of disease which are used in screening, diagnosis and monitoring of disease progression. Biomarkers used in risk prediction, screening and diagnostic tests are well established and offer distinct and obvious advantages. Molecular biomarkers have additional potential to identify individuals susceptible to disease. There are perhaps 100 blood-based biomarkers that are commonly recognised by physicians as important in disease prevention and treatment. Some familiar biomarkers include cholesterol, PSA, estrogen and glucose.

What is the significance of biomarkers in research?

Biomarkers are molecular, biological or physical characteristics that indicate a specific, underlying physiological state. They can be used to identify risk for disease, to make a diagnosis, to assess severity and identify the organs that are involved and guide treatment. Biomarkers can also be used in research-clinical studies to assess whether a drug is safe and effective as well as studies to learn more about health and disease.

Biotechnological and pharma companies are increa-singly looking into biomarkers to help R&D productivity and clinical trial success rate. They are using biomarkers as a tool to eliminate toxic compounds early in the development process, improve patient selection in clinical trials and improve the effectiveness of target validation by connecting it more closely with clinical outcomes. They also help create cellular assays for drug discovery AND Accelerate targeted therapy. For exampletrastuzumab (Genentech's Herceptin), imatinib mesylate (Novartis's Gleevec), and cetuximab (ImClone's Erbitux). Besides Biocon, Dr Reddy's Labs has taken the initiative to include biomarker evaluation studies in the development of its new drugs. Triesta Sciences, a company based out of Bangalore is doing extensive studies on biomarkers in oncology.

What are some conditions that act as biomarkers?

Cholesterol is perhaps the most well known biomarker and is an indicator of cardiovascular health. Other biomarkers include blood sugar, various metabolites, and proteins, plus physical measurements such as temperature and blood pressure, and medical imaging. Every lab test or X-ray doctor's order is a marker of what is going on with their patients, showing whether they are healthy, sick, getting better or getting worse. These examples are only the tip of the biomarker iceberg. Biological biomarkers for HIV/AIDS include viral load (the number of free virus particles in the blood) and the count of CD4-positive immune system cells. Fasting blood sugar and hemoglobin A1c, a protein that indicates a patient's blood sugar history, are established biomarkers for diabetes treatments.

What is the process of diagnosing diseases with the use of biomarkers?

Biomarkers depicting prodromal signs enable earlier diagnosis or allow for the outcome of interest to be determined at a more primitive stage of disease. Blood, urine, and cerebrospinal fluid provide the necessary biological information for the diagnosis. In these conditions, biomarkers are used as an indicator of a biological factor that represents either a sub-clinical manifestation, stage of the disorder, or a surrogate manifestation of the disease. Biomarkers used for screening or diagnosis also often represent surrogate manifestations of the disease. The potential uses of this class of biomarkers include identification of individuals destined to become affected or who are in the "pre-clinical" stages of the illness; reduction in disease heterogeneity in clinical trials or epidemiologic studies. They also aid in reflection of the natural history of disease encompassing the phases of induction, latency and detection and target for a clinical trial. The improvement in validity and precision far outweigh the difficulty in obtaining such tissues from patients.

What are the advantages of using biomarkers?

Biomarkers can reflect the entire spectrum of disease from the earliest manifestations to the terminal stages. Their use in research has grown out of the need to have a more direct measurement of exposures in the causal pathway of disease that is free from recall bias, and that can also have the potential of providing information on the absorption and metabolism of the exposures.

The rapid growth of molecular biology and laboratory technology has expanded to the point at which the application of technically advanced biomarkers will soon become even more feasible. Molecular biomarkers will, in the hands of clinical investigators, provide a dynamic and powerful approach to understanding the spectrum of neurological disease with obvious applications in analytic epidemiology, clinical trials and disease prevention, diagnosis, and disease management.

Are there any challenges in using biomarkers in drug discovery?

Biomarkers are usually surrogate markers for the progression or regression of the disease. They offer a means of coming to a quicker conclusion as to whether a particular drug or treatment may actually be working rather than wait for a very long time to see the real end point of the disease for eg death of a patient due to heart attack or cancer which may take many years.

However , it is very important for such surrogate markers to be validated adequately so that the conclusions as to whether the therapy or treatment is actually working can be relied upon. Validation of novel biomarkers is an extensive exercise involving many patients and following them over a long period of time. Such studies are usually published in scientific literature in peer reviewed journals. Once novel biomarkers have been validated they can then be used to quickly assess whether a new therapy is effective or not. That is their real value.

Several biomarkers are still waiting to be discovered. The opportunity in India is a large and diverse population which can offer a medical scientist, interested in biomarkers, access to a variety of patient samples and a statistically significant number of samples covering various stages of a particular disease. In other words our large population is at an advantage when it comes to discovering and validating new biomarkers.

editorial.ep@expressindia.com