cIAP2 as a therapeutic target in colorectal cancer and other malignancies.
Colorectal cancer is one of the most common malignancies worldwide and 70% of tumors are resectable, but patients with metastatic diseases cannot be cured with current treatment modalities. Inhibition of the apoptotic pathway is one of the factors that may be responsible for carcinogenesis and drug resistance, and the inhibitor of apoptosis protein (IAP) family is thought to prevent apoptosis through inhibition of direct caspases and pro-caspases. Recently an increasing amount of evidence has been accumulated regarding cIAP2 and other IAP proteins of the antiapoptotic pathway and NF-kappaB signal transduction. IAPs are abnormally regulated and expressed in the majority of human malignancies at elevated levels. As a result, they have recently been reported to be therapeutic targets. The downregulation of cIAP2 efficiently enhances apoptosis through the activation of caspase 3/7 and 5-fluorouracil (5-FU) sensitivity in colorectal cancer cells exposed to 5-FU. This report reviews the evidence for cIAP2 and other IAP molecules as a therapeutic target for malignancies including colorectal cancer. So far, the information on colorectal cancer is limited; so this study includes other malignancies as well, in order to summarize the current knowledge of drug development targeting IAP molecules and provide an overview of the future course.
Miura
Koh
K
Tohoku University Graduate School of Medicine, Department of Surgery, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. k-miura@surg1.med.tohoku.ac.jp
Karasawa
Hideaki
H
Sasaki
Iwao
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases
D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases