Combined Modularized Tumor Therapy—Tumor Biology—and Prognostic Factors: Bioengineering Tumor Response

Two rather different understandings of tumor pathophysiology exist; one is based on a reductionist or an observer’s point of view (‘bottom-up’ approach) and the other on an evolution-adjusted or a participator’s perspective (‘top-down’ approach). Important clinical requirements can be addressed by both ‘top-down’ and ‘bottom-up’ strategies. The first requirement is the incorporation of clinical knowledge derived from the application of different therapeutic methodologies; ‘top-down’ strategies, for instance, provide therapeutic access to communication-associated pathologies. The second requirement is overcoming limitations of ‘bottom-up’ strategies by focusing on the systematization of a tumor systems’ normativity. Such strategies involve the heterogeneity of the communicative expression of tumor-promoting pathways, the tumor-specific and stage-specific accessibility and distribution of targets among cellular compartments, the heterogeneity of chromosomal or molecular-genetic aberrations in stroma and tumor cells, the presence of basic mechanisms implementing robustness, and repair mechanisms. Information derived from biomodulatory therapy approaches may be translated into an alternative tumor classification on the basis of evolution-adjusted tumor pathophysiology. This translation and the generation of a novel response and prognostic markers will hopefully further the future development of novel combined modularized therapeutic strategies for overcoming the problems due to the cytogenetically and molecular-genetically defined heterogeneity of tumor and stroma cells.