Cancer continues to be a major challenge in medicine, as it remains the second leading cause of death in the United States, after heart disease, with a forecasted 1.7 million new cases in 2018. Finding new treatments remains a challenge, as illustrated by drug failures rates during clinical trial testing for non-small cell lung cancer (NSCLC; 89%), metastatic melanoma (83%) non-Hodgkin's lymphoma (92%) and prostate cancer (97%). In the face of this problem, developing anti-cancer agents demands new paradigms.

The addition of prognostic and predictive biomarkers, that predict disease progression and a patient's response to therapy, respectively, have offered promise in tackling the problem of developing new anti-cancer agents. Biomarker benefits potentially include more cost-effective use and diminishing the costs of development through better patient selection. Pioneering biomarker approved therapies include: HER2 in breast cancer, BCR-ABL in chronic myelogenous lymphoma, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements in NSCLC, BRAF V600 mutations in melanoma and the absence of RAS mutations in colorectal cancer.

Published studies to date on the potential benefits of biomarkers in oncology have lacked the analytical rigour, despite pointing to some positive trends. In addition, we have argued previously that biomarker use in clinical trial testing can entail new risks. The current strategy of combining new biomarkers that have never before been validated with a new drug may increase the risk of clinical trial failure. In theory, one would be compounding the probability that a new drug will fail to work with the probability that a new biomarker will fail to target appropriate patients for treatment.