Autophagy-A double-edged sword in oncology

Autophagy or "self-eating" digests proteins and functionless cell organelles to reuse. This cell-own recycling system attracts much attention in tumour biology. One of the major functions of autophagy is maintaining cellular homeostasis. Thus, it is constitutive active in all living cells. Damaged or dispensable proteins and organelles are removed to regulate composition and size of the cytoplasm. Many therapeutic treatments have been shown to modulate autophagy signalling although it is still unclear if autophagy represents a survival or a suicide mechanism for tumour cells. Tumour growth in response to blocked autophagy as well as tumour growth in response to induced autophagy has been described. Several recent review articles address the differential effect of autophagy manipulation to apoptosis signalling. However, less has been reported about interactions of autophagy manipulation to the outcome of cancer therapy and tumour growth. Therefore, this review tries to fill this gap. We discuss data demonstrating that cellular decisions to autophagy manipulation depend on tumour type, stage, microenvironment, autophagy initiator or inhibitor and combined tumour treatment. Finally, we come to the conclusion that further analyses are necessary before manipulation of autophagic mechanisms can find its way into tumour therapy for improved treatment of patients. (C) 2009 UICC