Targeting apoptosis pathways in cancer therapy

Irene M. Ghobrial, Thomas Elmer Witzig, Alex Adjei

Research output: Contribution to journalArticle

931 Citations (Scopus)

Abstract

Apoptosis, or programmed cell death, is a mechanism by which cells undergo death to control cell proliferation or in response to DNA damage. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy. These novel agents include those targeting the extrinsic pathway such as tumor necrosis factor-related apoptosis-inducing ligand receptor 1, and those targeting the intrinsic Bcl-2 family pathway such as antisense bcl-2 oligonucleotides. Many pathways and proteins control the apoptosis machinery. Examples include p53, the nuclear factor kappa B, the phosphatidylinositol 3 kinase pathway, and the ubiquitin/proteosome pathway. These can be targeted by specific modulators such as bortezomib, and mammalian target of rapamycin inhibitors such as CCI-779 and RAD 001. Because these pathways may be preferentially altered in tumor cells, there is potential for a selective effect in tumors sparing normal tissue. This article reviews the current understanding of the apoptotic pathways, including the extrinsic (cytoplasmic) and intrinsic (mitochondrial) pathways, and the agents being developed to target these pathways.

Original languageEnglish (US)
Pages (from-to)178-194
Number of pages17
JournalCa-A Cancer Journal for Clinicians
Volume55
Issue number3
StatePublished - May 2005

Fingerprint

Apoptosis
Neoplasms
Cell Death
Phosphatidylinositol 3-Kinase
NF-kappa B
Cytotoxins
Sirolimus
Therapeutics
Ubiquitin
Oligonucleotides
DNA Damage
Radiotherapy
Tumor Necrosis Factor-alpha
Cell Proliferation
Ligands
Proteins
temsirolimus
Bortezomib
Everolimus

ASJC Scopus subject areas

  • Oncology

Cite this

Targeting apoptosis pathways in cancer therapy. / Ghobrial, Irene M.; Witzig, Thomas Elmer; Adjei, Alex.

In: Ca-A Cancer Journal for Clinicians, Vol. 55, No. 3, 05.2005, p. 178-194.

Research output: Contribution to journalArticle

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