Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy

Bcl-2 protein plays a critical role in inhibiting anticancer drug-induced which is mediated by a mitochondria-dependent pathway that controls the of cytochrome c from mitochondria through anion channels. Constitutive pression of Bcl-2 or unchanged expression after treatment with anticancer confers drug resistance not only to hematologic malignancies but also to tumors. The down-regulation of Bcl-2 protein by the antisense (AS) (oblimesen sodium) may be a useful method for targeting the antiapoptotic and thereby increasing the chemotherapeutic effect of anticancer drugs. randomized, controlled, Phase III trials have compared standard with a combination of AS Bcl-2 and standard chemotherapy for the treatment patients with chronic lymphocytic leukemia, multiple myeloma, malignant noma, and nonsmall cell lung carcinoma. Nonrandomized clinical trials and clinical evaluations of AS Bcl-2 also are underway for patients with other nancies. Here, the authors review the current clinical and preclinical evaluations AS Bcl-2 and discuss its potential to act as a chemosensitizer and to enhance therapeutic effect of cancer chemotherapy. (C) 2004 American Cancer Society.