Patients expect approved drugs that work, are safe, and are “right” for them. Biomarkers can play a key role in making sure that this is the case.

The National Institutes of Health in the United States uses very precise language to define a biomarker: „A biomarker refers to a quantifiable biological parameter that is measured and evaluated as an indicator of normal biological, pathogenic, or pharmacologic responses to a therapeutic intervention.“

Sounds complicated, but it is not! While the term biomarker did not come into common usage until the 1970‘s, they have been integral to the practice of medicine for much longer. For example, recording a patient’s temperature is assessment of a biomarker for inflammation and possibly infection. There are many other well-established and familiar biomarkers. Blood pressure is routinely measured as part of routine physical examinations because high blood pressure has strong associations with stroke, heart attacks, and kidney disease. Blood tests for cholesterol are also carried out routinely because high cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), are strongly associated with cardiovascular disease. All of these biomarkers are measured because they have been repeatedly validated in large groups of patients and it has been demonstrated that therapies which change them can lower the risk for adverse clinical events (e.g., antihypertensive therapy significantly lowers both blood pressure and the risk for stroke).

Validation of new biomarkers helps in the development of more targeted interventions and evolution of disease management from trial and error to rationale therapy. This process is moving more rapidly in oncology than any other area of medicine. Therapies for multiple cancers are now selected on the basis of biomarkers on tumor cells (e.g., HER2 in breast cancer; EGFR, ALK, and PD-1 in lung cancer) and a recent analysis of >300 clinical trials in oncology indicated that use of a biomarker-based approach was associated with significantly improved outcomes (both response rate and progression-free survival). Studies that used targeted agents without a biomarker had negligible response rates.

It is also important to note that biomarkers may fall out of favor as we learn more about their relationships to clinical outcomes. For example, studies concerned with the relationship between lipids and cardiovascular events suggested residual clinical risk despite profound LDL-C lowering and several lines of evidence suggested that higher levels of high-density lipoprotein (HDL-C) – „the good cholesterol“ – reduced the risk for cardiovascular disease. This resulted in HDL-C becoming a target for therapy. However, more recent results from clinical and genetic studies have indicated that it is unlikely that raising HDL-C will be protective against coronary heart disease.

Identification and validation of new biomarkers goes hand-in-hand with development of new therapies and cooperation among the medical community, pharma companies, and regulators can accelerate the advancement of both processes.