title: Potential roles of antisense therapy in the molecular targeting of genes involved in cancer (review).
abstract: Recent advances in antisense methods targeting genes involved in cell proliferation, angiogenesis, and apoptosis provide a potential anticancer effect alone as well as in combination with drugs, and antisense therapy may be useful in overcoming drug resistance and increasing survival in patients with advanced cancer including those with solid tumors. In particular, antisense to Bcl-2 comprises a most promising therapy and is being tested in combination with anticancer drugs in randomized phase III trials for chronic lymphocytic leukemia, multiple myeloma, and malignant melanoma. The targeting of apoptosis-related proteins is promising for enhancing the effect of cancer chemotherapy. The molecular mechanism by which anticancer drugs induce apoptosis has been identified as mitochondrial dysfunction mediated by the release of cytochrome c. Modulation of multiple antiapoptotic signaling pathways involving Bcl-2 and Akt, which are related to growth factor-stimulated signal transduction in cell survival, is essential for enhancement of the cytotoxic effect of anticancer drugs. Herein, we review the current status of antisense therapy and its potential for enhancing anticancer drug-induced apoptosis.
authors.affiliation: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan. rkim@hiroshima-u.ac.jp
authors.forename: Ryungsa
authors.initials: R
authors.lastname: Kim
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tanabe
authors.forename: Manabu
authors.initials: M
authors.lastname: Emi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Uchida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toge
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051020:bcl-X Protein; D040262:Receptors, Vascular Endothelial Growth Factor