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… 
View on Nature
nature.com
10 Citations
Highly Influential Citations
1
Background Citations
3
Methods Citations
1

10 Citations

Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1
TLDR
Chemotherapeutic drugs can overcome protection afforded by Mcl-1 and A1 through endogenous Noxa protein in R CC cells, and the combination of such drugs with ABT-737 may be a promising strategy in RCC.
BCL-2 family antagonists for cancer therapy
TLDR
Preclinical and clinical data on several compounds that inhibit the interaction between BCL-2 family members and their natural ligand, a helical peptide sequence known as the BH3 domain are reviewed, and four criteria that define antagonists of the B CL-2 protein family are recommended.
Small molecules as pro-apoptotic anticancer agents.
  • P. Seneci
  • Biology
    Pharmaceutical patent analyst
  • 2012
TLDR
This review is chemically focused on small molecules and deals with five target families that influence caspase-dependent apoptosis: caspases-3, Bcl-2 and IAP protein family members, p53 and the proteasome.
Bcl‐xL represents a therapeutic target in Philadelphia negative myeloproliferative neoplasms
TLDR
The study suggests that Bcl‐xL plays an important role in MPN independently from JAK2 V617F mutation and demonstrates that targeting simultaneously JAK1 and Bcl-xL might represent an interesting new approach.
TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway.
TLDR
It is found that TW-37 induces cell growth inhibition and S-phase cell cycle arrest, with regulation of several important cell cycle-related genes like p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cycl in D1, and cyclin E.
Shock the heat shock network.
TLDR
The synthesis of Gamitrinibs is reported, which target mitochondrially localized HSP90, specifically killing human cancer cell lines, and provide a fresh approach for cancer treatment.
Targeting Mitochondria of Cancer Cells: Mechanisms and Compounds
TLDR
Mitochondria are being proposed and tested as plausible targets for cancer therapy because they comprise potent inducers of apoptosis, and their differences compared to mitochondria of normal cells give hope to the potential establishment of efficient and selective anti-cancer agents.
Mitochondrial fragmentation and neuronal cell death in response to the Bcl-2/Bcl-xL/Bcl-w antagonist ABT-737
Mitochondria: The Anti- cancer Target for the Third Millennium
TLDR
This work focuses on mitochondria-driven pathways by artemisinin and its derivatives, and Targets and strategies for the mitochondrial assault on cancer.
The mitochondrial death pathway: a promising therapeutic target in diseases
TLDR
The mitochondria are regulated by the BCL‐2 family proteins and mitochondrial membrane permeabilization and the role of caspases in MOMP is investigated.

References

SHOWING 1-8 OF 8 REFERENCES
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.
The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized.
A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells
TLDR
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
TLDR
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
TLDR
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.
Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins.
TLDR
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.
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis
TLDR
It is proposed that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2proteins to activate Bax and trigger apoptosis.
Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics.