Biomodulatory Therapy Approaches in Renal Clear Cell Carcinoma: A Perspective

The remarkable efficacy of multi-targeted biomodulatory therapies may be exemplarily shown in renal clear cell carcinoma (RCCC), particularly the biomodulatory activity of VEGFR-tyrosine kinase inhibitors and transcriptional modulators (pioglitazone and interferon-alpha). Biomodulation remodels tumor-immanent normative notions by therapeutically implementing non-normative boundary conditions in such a way that tumor control becomes possible. Normative notions in a tumor are morphological structures that are not only built differently in an evolutionary context, but are also evolutionarily constrained action norms, such as the hallmarks of cancer, and multifaceted patterns of inherent decision maxims, i.e., hubs and nodes. The biomodulatory activity of VEGFR-tyrosine kinase inhibitors is underlined (1) by different mechanisms of action dependent on the type of tumor (hepatocellular carcinoma, RCCC, de novo and relapsed acute myelocytic leukemia), (2) by profiles of side effects related to the type of tumor, and (3) by efficacy dependent on the metastatic organ site. The specific activity of transcriptional modulators in RCCC has been shown in recent phase II trials by the combined administration of pioglitazone and interferon-alpha. Established biomodulatory first-line therapies in RCCC need to be supplemented by further biomodulatory therapeutic principles for circumventing the following two dilemmas: The difficult combination of VEGFR-tyrosine kinase inhibitors with other classic targeted therapies because of cumulative toxicities, and the inefficacy of VEGFR-tyrosine kinase inhibitors in patients with bone (about 30 %) and brain (4–48 %) metastases from RCCC. As shown in clinical trials, multi-targeted biomodulatory therapy approaches have in principle the ability to induce continuous complete remission in metastatic renal clear cell carcinoma at a low rate of side effects.