Identification and Characterization of a Small Molecule Bcl-2 Functional Converter.

Cancer cells exploit the expression of anti-apoptotic protein Bcl-2 to evade apoptosis and develop resistance to therapeutics. High levels of Bcl-2 leads to sequestration of pro-apoptotic proteins causing the apoptotic machinery to halt. In this study, we report discovery of a small molecule, BFC1108 (5-chloro-N-(2-ethoxyphenyl)-2-[(4-methoxybenzyol)amino]benzamide), which targets Bcl-2 and converts it into a pro-apoptotic protein. The apoptotic effect of BFC1108 is not inhibited, but rather potentiated, by Bcl-2 overexpression. BFC1108 induces a conformational change in Bcl-2, resulting in the exposure of its BH3 domain both in vitro and in vivo. BFC1108 suppresses the growth of triple-negative breast cancer xenografts with high Bcl-2 expression and inhibits breast cancer lung metastasis. This study demonstrates a novel approach to targeting Bcl-2 using BFC1108, a small molecule Bcl-2 functional converter that effectively induces apoptosis in Bcl-2-expressing cancers. SIGNIFICANCE: We report the identification of a small molecule that exposes the Bcl-2 killer conformation and induces death in Bcl-2-expressing cancer cells. Selective targeting of Bcl-2 and elimination of cancer cells expressing Bcl-2 opens up new therapeutic avenues.

Laboratory monitoring in oncology.

OBJECTIVES: To educate pharmacists about the application of laboratory values in oncology. METHODS: Research on drugs used in cancer therapy was conducted using multiple sources, including primary, secondary and tertiary references. Online searches were conducted on Medline (1966-2004), EMBASE (1996-2004) and Ovid databases, using a drug's generic name and key words, such as 'adverse effects', 'hematotoxicity', 'renal toxicity', 'hepatotoxicity', 'cardiotoxicity', 'organ dysfunction', and terms describing chemotherapy-related toxicity, such as 'tumour lysis syndrome'. RESULTS: Laboratory monitoring in oncology was separated into the hematologic, hepatic, renal, cardiovascular and pulmonary systems. Laboratory tests applicable to each system are discussed. In addition, tests pertaining to specific drugs used in cancer therapy are explained. This information was compiled into a comprehensive continuing pharmacy education module. CONCLUSION: Laboratory monitoring assists the pharmacist in the monitoring of chemotherapy. A general understanding of common tests used in cancer therapy and knowledge specific to drugs used can help the pharmacist tailor drug therapy monitoring.