The increasing knowledge on the molecular pathogenesis of cancer has led to the development of a wide spectrum of targeted treatment approaches. Key targets are molecules belonging to signaling pathways involved in the regulation of cell survival, proliferation, invasion and spread of malignant cells. Central regulators in the context of cell survival are molecules involved in the regulation of programmed cell death, epidermal growth factor receptor pathways and regulators of the tumor microenvironment. The inhibition of the epidermal growth factor receptor has already become an accepted approach. In contrast to that, direct interference with cell death signaling, i.e. death receptor based approaches and the inhibition of Bcl proteins, is still subject to clinical testing. Regarding the therapeutic modulation of the tumor microenvironment the primary drug targets are those molecules involved in the interaction of malignant cells with the surrounding normal stromal cells and/or with the extracellular matrix. Currently, inhibition of neo-angiogenesis and the blocking of intergrin-mediated adhesion of malignant cells to the surrounding tissue have entered clinical practice or are in advanced phases of clinical testing. The common denominator of all these approaches is to try to specifically target the tumor with no or minimal interference of normal tissue function. The side-effects of molecular targeted drugs fundamentally differ from those of the conventional oncological methods, such as radiotherapy and cytotoxic chemotherapy. However, for the majority of these targeting agents, clinical testing has unfortunately found only slight efficacy when used as a monotherapy. Thus, the combination of these substances with proven oncological procedures and the integration into highly complex multimodal protocols is urgently needed to evaluate the therapeutic surplus of the multitude of newly developed agents. The aim of the current article is to give a short overview of the current status of targeted interference with cell death signaling and neighboring fields.
