Tumor biology and experimental therapeutics.

Recent research using multicellular tumor spheroids has resulted in new insights in the regulation of invasion and metastasis, angiogenesis and cell cycle kinetics. The onset and expansion of central necrosis in tumor spheroids has been characterized to be a complex interaction of several mechanisms; in a number of cases, necrosis is not a consequence of hypoxia or anoxia, but emerges as secondary necrosis following an accumulation of apoptosis in spheroids. Recent therapeutically oriented studies have been directed towards novel hypoxic markers, targeted therapy, multicellular-mediated drug resistance, and heavy ion irradiation of spheroids. Research efforts should be enhanced mainly in the fields of tumor tissue modeling by heterotypic three-dimensional (3D) cultures and of apoptotic versus necrotic cell death. Based on the fundamental differences between monolayer and 3D cultures, spheroids should become mandatory test systems in therapeutic screening programs.