Human turnor cells grown in threedimensional multicellular spheriod culture represent an ideal system to study the heterogeneous interaction between microenvironment and different therpeutic modalities in patients. Overcoming this hetergenenity is the most challeging task for the improvement of cancer theraphy. Examples of this interaction are given with the meaning of pO2 and pH for the treatment of tumor cells with radition cytostatic,cytokines and gene therapy. The presented result might form a base for the use of muticellular spheriods in a concerted action between clinicians, biologist and mathematicians to improve tumor therapy individually for patient.