Epigenetic-based companion diagnostics

In current medical practice, when a patient is diagnosed with cancer the treating physician generally follows a standard protocol, assigning the treatment that gives a favorable response in the largest proportion of patients. However, in many individual instances this approach may not be the most effective solution and, typically, treatment is only initiated or altered once the cancer has actually started progressing. During this process, patients will lose treatment time waiting to start chemotherapy or will endure severe side effects associated with toxic chemotherapeutic treatments. While some patients are undertreated because current diagnostic methods cannot provide accurate enough information regarding the aggressiveness or drug response of their disease, others with nonaggressive forms of cancer are overtreated and unnecessarily undergo the side effects associated with chemotherapeutic treatment. Epigenetic markers have been widely investigated and are considered key regulators of cellular transcription. Histone modifications and DNA methylation have been demonstrated to play key roles in maintaining stem-cell-like states, cellular differentiation and cancer. In particular, DNA methylation is a frequent, abundant and stable cancer mark, with an inherent role in oncogenesis and tumor progression. In this article, the potential of DNA methylation as a companion diagnostic is assessed, illustrated by exploring some development paths. Epigenetic silencing of MGMT is a key example of how biomarker development, biological pathways and clinical utility come together, serving as a hallmark of epigenetic companion diagnostics.