Multiple cell death pathways as regulators of tumour initiation and progression

Acquired defects in signalling pathways leading to programmed cell death (PCD) are among the major hallmarks of cancer. Although focus has been on caspase-dependent apoptotic death pathways, evidence is now accumulating that nonapoptotic PCD also can form an important barrier against tumour initiation and progression. Akin to the earlier landmark discoveries that lead to the identification of the major cancer-related proteins like p53, c-Myc and Bcl-2 as controllers of spontaneous and therapy-induced apoptosis, numerous proteins with properties of tumour suppressors and oncoproteins have recently been identified as key regulators of alternative death programmes. The emerging data on the molecular mechanisms regulating nonapoptotic PCD may have potent therapeutic consequences.