Bim-targeted cancer therapy: a link between drug action and underlying molecular changes.
In the past few years, the pro-apoptotic molecule Bim has attracted increasing attention as a plausible target for tumor therapy. A variety of normal and pathological systems regulated by Bim, dependent on cell type, apoptotic stimulation, and chemotherapeutic agents, have been documented. Bim promotes anoikis of many tumor cells, such as lung cancer, breast cancer, osteosarcoma, and melanoma. Various chemotherapeutic agents use Bim as a mediating executioner of cell death. Hence, Bim suppression supports metastasis and chemoresistance. Imatinib, gefitinib, bortezomib, and Bim protein itself are spotlighted as current and future Bim-targeting therapeutic agents. The potential benefits of Bim-targeted therapies are selectivity of treatment for tumor cells and reduction in tumor-associated phenomena such as chemoresistance and metastasis. Thus, Bim-targeting therapies may provide more effective and unique tumor management modalities in future. This review article discusses all these issues.
Akiyama
Toru
T
Department of Orthopaedics, University of Melbourne, and St. Vincent's Hospital Melbourne, L3-Daly Wing, 35 Victoria Pde., Fitzroy, Melbourne, VIC 3065 Australia.
Dass
Crispin R
CR
Choong
Peter F M
PF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D054875:Ubiquitination / Q000187:drug effects
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D045304:Cytochromes c