Targeting apoptosis pathways through the design of small-molecule inhibitors are being pursued as novel cancer therapeutic approaches. A number of classes of small-molecule inhibitors designed to directly target key apoptosis regulators, including Bcl-2/Bcl-xL inhibitors, MDM2 inhibitors and IAP inhibitors, are now in clinical development. Preclinical and clinical studies have shown that both de novo and acquired resistance to these novel agents is common. Therefore, understanding the underlying molecular mechanism of action for drug resistance is critical for the successful development of these novel agents. Herein, we will present our recent findings using both in vitro and in vivo models. Our data have provided novel insights into the mechanism of drug resistance and effective strategies to overcome such resistance.

Understanding and overcoming resistance of MDM2 and Bcl-2/Bcl-xL small-molecule inhibitors in human cancer

245th National Meeting (2013)

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