ABT-737, proving to be a great tool even before it is proven in the clinic

@article{Vaux2008ABT737PT,
  title={ABT-737, proving to be a great tool even before it is proven in the clinic},
  author={David L. Vaux},
  journal={Cell Death and Differentiation},
  year={2008},
  volume={15},
  pages={807-808}
}
  • D. Vaux
  • Published 1 May 2008
  • Biology
  • Cell Death and Differentiation
The remarkable growth in interest in apoptosis began when inhibition of cell death was linked to human cancer, and components of the mechanism for cell death were identified, beginning with recognition that the product of the bcl-2 gene, which is activated in follicular lymphoma, is an inhibitor of cell death.1 However, the resulting avalanche of publications also brought confusion and controversy, especially when mechanisms of cell death were inferred from the morphological appearance of dying… 
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An inhibitor of Bcl-2 family proteins induces regression of solid tumours
TLDR
Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation.
A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells
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A new paradigm of apoptosis in primary B-cell malignancies is described, whereby targeting of BCL2 results in all the classical features of apoptotic together with OMM rupture independent of caspase activation.
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
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Results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.
Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die
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Apoptosis after growth factor withdrawal or drug treatment is associated with mitochondrial cytochrome c release and activation of Apaf-1 and caspase-9 and transfection with Bcl-2 provided long-term, clonogenic protection, and could act independently of the apoptosome.
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The results indicate that Bak is held in check solely by Mcl-1 and Bcl-x(L) and induces apoptosis only if freed from both, and the finding that different prosurvival proteins have selective roles has notable implications for the design of anti-cancer drugs that target the B cl-2 family.
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