Molecular testing in oncology: problems, pitfalls and progress.
Recent advances in the understanding of the molecular basis of cancer and the development of molecular diagnostics based on this knowledge have done much to progress the fields of oncology and pathology. Technological developments such as Next Generation Sequencing (NGS) and multiplex assays have made feasible the widespread adoption of molecular diagnostics for clinical use. While these developments and advances carry much promise, there are pitfalls to implementing this testing. Choosing appropriate biomarkers is a vital first step for clinical use and being able to understand the complex relationship between predictive and prognostic biomarkers is a crucial component of this. Testing for standard of care biomarkers is not straightforward, one must choose carefully between clinical trial assays, assays that analyse the same biological phenomenon or surrogate biomarkers. Sample heterogeneity and population specific difference is assays may skew results and must be controlled for at the assay design stage. At a technical level, NGS has the potential to revolutionise laboratory practice and approaches to cancer treatment. However, use of this technology requires careful planning and implementation if one is to avoid technical and ethical quagmires. Finally, with FDA regulation of companion diagnostics one may be limited to therapy specific assays.
Cancer Molecular Diagnostics, St. James's Hospital, Dublin 8, Ireland; Department of Histopathology, St. James's Hospital, Dublin 8, Ireland; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland. Electronic address: obriec12@tcd.ie.
Cathal P
CP
O'Brien
Department of Obstetrics and Gynecology, Magee-Womens Hospital, University of Pittsburgh Medical Center, 300 Halket Street, Pittsburgh, PA 15213, USA.
Sarah E
SE
Taylor
Department of Histopathology, St. James's Hospital, Dublin 8, Ireland; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland; Department of Histopathology, The Coombe Women and Children's Hospital, Dublin 8, Ireland.
John J
JJ
O'Leary
Cancer Molecular Diagnostics, St. James's Hospital, Dublin 8, Ireland; Department of Histopathology, St. James's Hospital, Dublin 8, Ireland; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland.
Stephen P
SP
Finn
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D033161:Government Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008495:Medical Oncology / Q000379:methods* / Q000639:trends; D025202:Molecular Diagnostic Techniques; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics; D014481:United States; D014486:United States Food and Drug Administration
D014408:Biomarkers, Tumor
Alk; Biomarker; EGFR; Lung cancer; Molecular diagnostics; NGS