Targeting Protein Dynamics in Lymphoma

Every cancer cell can be characterized by its ability to make lots of different proteins, which collectively can contribute to the misbehavior of the cancer cell.  This notion was first vetted and established with the development of the proteasome inhibitor bortezomib.  This novel class of drugs, originally developed to treat cachexia associated with cancer, were developed because they inhibited the cells ability to recycle protein.  Our group was among the first to demonstrate the activity of bortezomib in lymphoma, eventually leading to its approval in mantle cell lymphoma.  The accumulation of certain types of protein in the cell is thought to directly lead to cell death.  While there are a host of other effects mediated by proteasome inhibitors which can account for their activity in lymphoma, the accumulation of misfolded proteins and protein aggregates has been postulated to be among one of the more important mechanisms of cell death mediated by these drugs.