With the recent attention the MAPK-Elk1 axis has attracted and the evidence supporting STAT3 and cJun as potential therapeutic targets, we propose the three transcription factors as molecules of a significant role in the emergence of Bortezomib resistance, the targeting of which could truly improve the management of prostate cancer cases by expanding our drug repertoire and disease understanding. This evidence concerns the gene ELK1 and Familial prostate cancer.