A Practical Approach to Tumor Heterogeneity in Clinical Research and Diagnostics

This Pathobiology issue tries to better define the complex phenomenon of intra-tumor heterogeneity (ITH), mostly from a practical point of view. All this because ITH represents a central issue in oncology development and has to be investigated directly in patients’ tissues with immediate application to today patient’s treatment. Different types of ITH should be considered: the clonal genetic and epigenetic evolution, the morphologic heterogeneity and tumor sampling, the heterogeneity from micro-environmental autocrine and paracrine interaction and the stochastic plasticity related to different functional cell efficiencies. For a higher level of reproducibility in clinical research and diagnostics it is necessary to establish standardized analytical methods, included microdissection. In situ techniques can be pivotal to explore tumor micro-environment and can be ameliorated with associated digital analysis. Liquid biopsies for plasma DNA analysis are at present the best method to study recurrent tumors with treatment adaptation and a diffuse clinical use could be beneficial. The different types of tumor genomic instabilities could have a pragmatic application to rank ITH for clinical applications: patients with high nucleotide mutation rate can have different treatment approaches than patients with high copy number alterations.