ONCOLOGY Vol 18 No 14_Suppl_11

Proteasome inhibition is a novel, targeted approach in cancertherapy. Both natural and synthetic proteasome inhibitors selectivelypenetrate cancer cells, disrupting the orderly destruction of key regulatoryproteins involved in tumorigenesis and metastasis. Disrupting theorderly destruction of regulatory proteins causes an imbalance of theseproteins within the cell, which interferes with the systematic activationof signaling pathways required to maintain tumor cell growth and survival;therefore, cellular replication is inhibited and apoptosis ensues.

Bortezomib (PS-341, Velcade) is a novel, first-in-class proteasomeinhibitor with antitumor activity against a number of hematologic andnonhematologic malignancies.

Throughout my career, I have collaborated with manycolleagues who share a common goal of mappingand reversing the molecular mechanisms involvedin the malignant transformation of plasma cells and resistanceof myeloma cells to chemotherapy drugs. Over theyears, I have had the privilege of participating in andwitnessing the discovery of numerous promising moleculartargets, which has led to the development of manyunique antitumor drugs; however, the marketing of a compoundthat significantly impacts the lives of cancer patientsis still rare.