Table 1

Apoptosis-triggering strategies

StrategyTargetApproachStage of development
Proapoptotic approaches
Introduction of proapoptotic playersTRAILRecombinant proteinClinical trials planned
ApoptinGene therapyPreclinical
CaspasesGene therapyPreclinical
Modulation of antiapoptotic genes or pathwaysMitochondria:
Proapoptotic molecules (Bax, BCL-Xs)Gene therapyPreclinical
Downregulate antiapoptotic molecules (Bcl-2, Bcl-XL)ODNsPhase II/III
Direct effect on mitochondriaLonidamine, arsenitePhase III
Direct effect on poresPK 11195Preclinical
Restoration or manipulation of tumor suppressor genesp53Gene therapyPhase II/III
RetinoblastomaGene therapyPreclinical
FHIT Gene therapyClinical trials planned
Permissive approaches
OncogenesPI3kLY294002Preclinical
RasSmall molecules, ODNsPhase II/III
BCR-ABLSmall molecule (STI-571)Phase III
NFκBODNsPhase I/II
Proteasome inhibitorsPS-341Phase II
c-rafODNsPhase II
c-mybODNsPreclinical
Cell cycle modulatorsUCN-01, flavopiridolPhase III