Open AccessTargeting Apoptosis Pathways in Cancer Therapy
Author(s) -
Ghobrial Irene M.,
Witzig Thomas E.,
Adjei Alex A.
Publication year - 2005
Publication title -
ca: a cancer journal for clinicians
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 62.937
H-Index - 168
eISSN - 1542-4863
pISSN - 0007-9235
DOI - 10.3322/canjclin.55.3.178
Subject(s) - apoptosis , programmed cell death , microbiology and biotechnology , signal transduction , cancer research , biology , bortezomib , pi3k/akt/mtor pathway , kinase , intrinsic apoptosis , proteasome , cancer cell , cancer , caspase , immunology , biochemistry , genetics , multiple myeloma
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.