Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics—Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer

Abstract

Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

Applications of molecular testing in surgical pathology of the head and neck

“…As a general category, these markers are often referred to as 'companion diagnostics.' [34][35][36] Companion diagnostics have received national press in the past few years because of the Food and Drug Administration's proposal to implement oversight laboratory developed tests, with a particular focus on companion diagnostics. 4,37,38 In head and neck cancer, relatively few companion diagnostic assays are used in the routine clinical setting.…”

Staging, Tumor Profile, and Prognostic Groups in Lung Cancer or the New Tower of Babel

“…Still others are merely prognostic with no effective targeted therapies, such as mutation of the Kirsten rat sarcoma viral oncogene homolog gene (KRAS). 11 These tumor characteristics enhance our capacity to refine prognosis for a given patient, but they do not provide us with any additional information on the anatomic extent of the tumor. Therefore, tumor profile cannot enhance staging.…”

The Genomic Era of Clinical Oncology: Integrated Genomic Analysis for Precision Cancer Care

“…This could be accomplished with lowthroughput "hotspot" assays; however, a high-throughput NGS approach that can detect EGFR sensitizing and resistance mutations as well as mutations in other genes, such as KRAS, which may alter patient response to EGFR inhibitors, providing further clinical advantages. Additionally, detection of chromosomal rearrangements in ALK and ROS1 genes as well as overexpression/increased copy number of the MET gene is critical because patients with these genomic alterations have shown significant response to ALK inhibitors [Keedy et al, 2011;Korpanty et al, 2014;Plönes et al, 2016]. Overall, specific targeting of tumors with alterations in these genes leads to better patient outcomes and increased survival, especially in those patients with metastatic disease [Keedy et al, 2011;Korpanty et al, 2014].…”

“…The standard of care for patients with these tumors is to perform molecular testing for mutations in the EGFR gene to assess sensitivity to FDA-approved EGFR inhibitors [Dietel et al, 2015;Plönes et al, 2016]. This could be accomplished with lowthroughput "hotspot" assays; however, a high-throughput NGS approach that can detect EGFR sensitizing and resistance mutations as well as mutations in other genes, such as KRAS, which may alter patient response to EGFR inhibitors, providing further clinical advantages.…”

“…All of these aberrations can be directly tested by NGS methods using a combination of DNAand RNA-based panels for SNVs, indels, fusions, and CNVs. However, at this time only certain methods and products have been FDA approved as companion diagnostics for testing and certain results obtained by NGS methods may require orthogonal testing confirmation for treatment in the US [Dietel et al, 2015;Plönes et al, 2016].…”