33IN - What are the New Tools Available?

Abstract

ABSTRACT Extensive sequencing, expression profiling, and recently epigenetic analyses have generated a wealth of data resulting in improved knowledge about molecular pathogenesis of all major tumor entities. Still major challenges remain: How can we translate this knowledge into clinically meaningful diagnostic targets and assays? How can molecular diagnostics contribute to improved personalized tumor therapy? Are we looking at the right collectives? Dramatic improvement has been made in clinical-diagnostic application: a nearly complete arsenal is available for detecting treatment relevant molecular changes in tumor tissue. About half of our assays is based on on-slide analyses (immunohistology, FISH/CISH) and this will remain for the foreseeable future. We have established quality assured conditions for Next Generation Sequencing even on smallest paraffin-embedded tissue specimen (Endris et al., 2014), assembled long-standing diagnostic experience, and performed roll-out and quality assurance measures. These concerted diagnostic activities are essential for recent ‘umbrella concepts’ (such as the ‘Liver Cancer Center Heidelberg’ and ‘STRICT’) joining clinical service and innovative trial concepts to efficiently allocate patients to systemic treatment options and clinical trials. These recent concepts demonstrate that current data from comprehensive profiling efforts, such as ICGC/TCGA are biased by two means: they are derived from resected tumors thus representing a better prognostic group amenable to curative treatment; furthermore DNA-based data are surrogates for therapy relevant protein changes that in frequently show significant deviations. Therefore, profiling of collectives of progressed tumors will provide better data for current and future targeted therapy. A new comprehensive concept integrating exploratory profiling, targeted molecular pathology analyses, clinical trial portefolios including recalling, active patient databases and bedside-bench translational research is necessary to improve personalized treatment approaches and will be outlined. Disclosure: The author has declared no conflicts of interest.