Bcl-2-related antisense therapy.
High expression of the bcl-2 proto-oncogene is found in various human hematologic malignancies and solid tumors. Bcl-2 protein exerts its oncogenic role by preventing tumor cells from undergoing apoptosis induced by radiation, chemotherapy, and hormonal therapy. Antisense oligonucleotides directed toward the open reading frame of the bcl-2 gene have been used to inhibit Bcl-2 expression. Inhibition of Bcl-2 expression sensitizes lymphoma and leukemia cells to radiation and chemotherapy. However, it remains to be determined whether Bcl-2 antisense oligonucleotides will have a beneficial effect in solid tumors, such as breast cancer. Laboratory results indicate that Bcl-2 overexpression induces endocrine and chemoresistance in breast cancer cells. However, high levels of Bcl-2 have been associated with favorable prognostic factors, suggesting that Bcl-2 may not be an appropriate target in breast cancer. We will discuss the paradoxical role of Bcl-2 and the potential therapeutic application of Bcl-2 antisense oligonucleotides in breast cancer.