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Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells

Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells
Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells
Apoptosis (or programmed cell death) is a genetically controlled “cell suicide” pathway which plays an essential role in deleting excess, unwanted or damaged cells during development and tissue homeostasis. Dysregulation of apoptosis contributes to a wide variety of pathological conditions, including AIDS, cardiovascular disease, infectious disease, autoimmunity and neurodegenerative disorders. Resistance to apoptosis is also a common feature in human malignancies, contributing to both the development of cancer and resistance to conventional therapies such as radiation and cytotoxic drugs, which function by activating apoptotic cell death pathways. Bcl-2 is one of the best characterized cell death control proteins; its overexpression confers resistance to a broad range of apoptosis inducers and the cell survival functions of Bcl-2 are activated by translocation in lymphomas and overexpression in many other cancer types. A wealth of experimental data supports the idea that Bcl-2 is an attractive and tractable target for newer molecularly directed anti-cancer strategies, designed to promote cancer cell death. Here we review current understanding of the mechanism of action and importance of Bcl-2 in cancer cells and progress in developing new agents to target this key survival molecule.
0929-8673
1031-1039
Osford, S.M.
d16e759d-eefa-4c69-8c64-8ddcd036b9e2
Dallman, C.L.
ef0f1787-ca9a-498e-a430-5ba3a97e2d6d
Johnson, P.W.
e01f93bd-4ce9-473a-991c-b770f4a6029b
Ganesan, A.
62aa5a87-9308-4383-8686-99726b6bcfb9
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Osford, S.M.
d16e759d-eefa-4c69-8c64-8ddcd036b9e2
Dallman, C.L.
ef0f1787-ca9a-498e-a430-5ba3a97e2d6d
Johnson, P.W.
e01f93bd-4ce9-473a-991c-b770f4a6029b
Ganesan, A.
62aa5a87-9308-4383-8686-99726b6bcfb9
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394

Osford, S.M., Dallman, C.L., Johnson, P.W., Ganesan, A. and Packham, G. (2004) Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells. Current Medicinal Chemistry, 11 (8), 1031-1039.

Record type: Article

Abstract

Apoptosis (or programmed cell death) is a genetically controlled “cell suicide” pathway which plays an essential role in deleting excess, unwanted or damaged cells during development and tissue homeostasis. Dysregulation of apoptosis contributes to a wide variety of pathological conditions, including AIDS, cardiovascular disease, infectious disease, autoimmunity and neurodegenerative disorders. Resistance to apoptosis is also a common feature in human malignancies, contributing to both the development of cancer and resistance to conventional therapies such as radiation and cytotoxic drugs, which function by activating apoptotic cell death pathways. Bcl-2 is one of the best characterized cell death control proteins; its overexpression confers resistance to a broad range of apoptosis inducers and the cell survival functions of Bcl-2 are activated by translocation in lymphomas and overexpression in many other cancer types. A wealth of experimental data supports the idea that Bcl-2 is an attractive and tractable target for newer molecularly directed anti-cancer strategies, designed to promote cancer cell death. Here we review current understanding of the mechanism of action and importance of Bcl-2 in cancer cells and progress in developing new agents to target this key survival molecule.

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Published date: 2004

Identifiers

Local EPrints ID: 26505
URI: http://eprints.soton.ac.uk/id/eprint/26505
ISSN: 0929-8673
PURE UUID: 1c70a009-dd50-468d-829c-c184d7c6569c
ORCID for G. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 21 Apr 2006
Last modified: 23 Jul 2022 01:46

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Contributors

Author: S.M. Osford
Author: C.L. Dallman
Author: P.W. Johnson
Author: A. Ganesan
Author: G. Packham ORCID iD

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