Background: Tailoring treatment strategies to individual patients requires the availability of reliable biomarkers. Despite important investment in biomarker research, few examples of successful biomarker-drug co-development are currently seen in clinical practice. The validity of a biomarker measurement may be affected by different pre-analytical, analytical and post-analytical factors. The lack of control or oversight of any of these factors may ultimately lead to failure in translating a promising research finding into clinical practice. In the present review, we put into perspective some of the obstacles to "precision" oncology, focusing on the technical and biological hurdles that may affect the validity of a biomarker result and, ultimately, the likelihood of a new targeted agent to reach the clinic.
Conclusion: Biomarker application in precision oncology must consider the evolution of neoplastic disease, evaluate strengths and limitations of the platform used for the determination, and efficiently address specimen type and handling issues. In-depth analytical validation of a new biomarker test that includes evaluation of target stability should be performed before the test is used in clinical samples. More efficient sampling and use of high-sensitivity methodologies may overcome the influence of tumor heterogeneity on biomarker measurement. Clinical trials with biomarker endpoints may only be successful when multidisciplinary academic study teams are involved and results meet the highest quality standards.