10.4225/03/5982604089157
RICHARD JOSEPH REBELLO
RICHARD JOSEPH
REBELLO
Targeting the ribosome to treat advanced prostate cancer
Monash University
2017
Prostate
MYC
PIM
Ribosome
Cancer Cell Biology
Cancer Therapy (excl. Chemotherapy and Radiation Therapy)
2017-08-02 23:29:02
Thesis
https://bridges.monash.edu/articles/thesis/Targeting_the_ribosome_to_treat_advanced_prostate_cancer/5263501
Metastatic castrate-resistant prostate cancer (mCRPC) remains incurable, highlighting the need for new therapeutic targets. Prostate epithelium is exquisitely sensitive to MYC activity and MYC is universally overexpressed in mCRPC. One key process in cancer cells is to accelerate growth via stimulation of high levels of ribosome biogenesis through regulation of RNA polymerase I (Pol I). This thesis describes preclinical evidence that co-targeting Pol I transcriptional activity and PIM kinases is an effective means of inhibiting MYC-driven prostate cancer. We employ numerous pre-clinical models of PC which shows the efficacy of therapies that combine to target MYC-directed signaling to the ribosome.