Bcl-2 antisense oligonucleotides: a potential novel strategy for the treatment of breast cancer.
Bcl-2 is an inhibitor of apoptosis and is overexpressed in more than half of all human cancers. Overexpression of Bcl-2 occurs in 40% to 80% of human breast tumors. Bcl-2 is not an independent prognostic marker in breast cancer patients, in part because most Bcl-2-positive breast cancers express estrogen and/or progesterone receptors. This positive association of Bcl-2 with hormone receptors in breast cancer may explain its apparent correlation with response to hormone therapy. However, diminished apoptotic response caused by Bcl-2 overexpression is associated with cellular resistance to chemotherapeutic drugs. Downregulation of bcl-2 by antisense oligonucleotides has been shown to improve the efficacy of chemotherapy in experimental models. Phase III randomized clinical trials are ongoing in patients with solid tumors. Bcl-2 antisense-based therapy represents a viable strategy for inducing apoptosis and enhancing the chemosensitivity of breast cancers.
Nahta
Rita
R
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Esteva
Francisco J
FJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D013873:Thionucleotides / Q000627:therapeutic use
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C408162:oblimersen