Dr. Rodger Tiedemann, PhD, ChB, MB, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto Interview date: October 18, 2013 

Dr. Rodger Tiedemann describes why proteasome inhibitors are useful to treat myeloma but will never be a cure for myeloma. He shares how they are more like a persnickety goat, eating the weeds and flowers of the myeloma, but never touching the root. He explains his findings that genes IRE1 and XBP1 cause stress in the plasma cells, which create the M-spike. Interestingly, the earlier progenitor cells don't have this XBP1 gene and are less sensitive to this class of drugs. He shares how proteasome inhibitor resistance can be either resistance from the get-go before any treatment is given or resistance that is acquired over the life of treatment.  He takes us back to 10th grade biology and explains the hierarchy of cell production: stem cells regenerate both new stem cells and also multiple layers of progenitor cells, which eventually become plasma cells. He describes his next step to screen drugs to see which ones affect the earlier progenitor cells before they turn into plasma cells to hit both early and later stage myeloma cells. He describes the 8 sub-types of myeloma and describes his search for genes that affect myeloma growth - how he has used RNA screening of 8,000 possible genes to find a short-list of messenger genes that are signaling myeloma cell growth. He shares an open clinical trial that targets the signaling shutdown of one of these genes (XPO1), a drug that essentially "kills the messenger." He also describes an additional study of his trying to accomplish two things at once: using busulphan and melphalan together before transplant to improve impact on remission and at the same time looking at the impact on progenitor cells. He explains how he is able to overcome past toxicity issues by adjusting the dose of busulphan for patients individually. The live mPatient Radio podcast with Dr. Rodger Tiedemann