Bcl-2 antisense therapy in B-cell malignant proliferative disorders.
Overexpression of Bcl-2 oncogene has been clinically associated with an aggressive clinical course, chemotherapy and radiotherapy resistance, and poor survival in patients with malignant B-cell disorders. Patients with relapsed or refractory chronic lymphocytic leukemia, multiple myeloma, or non-Hodgkin's lymphoma have limited therapeutic options. Preclinical and early clinical data have shown that Bcl-2 oncoprotein can be decreased by Bcl-2 antisense therapy. Also, downregulation of Bcl-2 protein can result in reversal of chemotherapy resistance and improved antitumor activity of biologic agents. Various clinical trials are evaluating the role of targeting Bcl-2 as a mechanism to enhance the antitumor potential of chemotherapy and immunotherapy. Early results from these clinical studies are encouraging and confirm the proof of principle for antisense therapy. As current data mature, these trials will hopefully validate preliminary results and establish Bcl-2 antisense as an important addition to the current armamentarium used in the treatment of patients with B-cell neoplasms.
Chanan-Khan
Asher
A
Department of Medicine, Lymphoma/Myeloma Section, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. asher.chanan-khan@roswellpark.org
Czuczman
Myron S
MS
D014408:Biomarkers, Tumor / Q000032:analysis; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2