Signaling cascades in the progression of multiple myeloma. Following a primary event (eg, chromosome translocation involving immunoglobulin genes), activation of a variety of secondary signaling cascades (MAPK, STAT3, and Akt are shown in random order) is associated with tumor progression. In certain tumors, blockade of 1 pathway (by the Akt inhibitor akti-1/2, for example) inhibits growth and induces apoptosis. Given intratumor heterogeneity, it seems likely that alternative pathways associated with drug resistance (denoted by an X) will eventually be activated and that combined blockade of the signaling cascades may be more effective.