The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer
2017
Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is characterized by genomic
structural variationswith relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR) and
ribosome biogenesishas been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The
poly(
ADP-ribose)
polymerase(
PARP)
inhibitor
olaparibhas been approved to treat women with defects in HR due to germline
BRCA mutations. Recent evidence demonstrated the efficacy of targeting
ribosome biogenesiswith the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC)-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting
ribosome biogenesisas a novel therapeutic approach against HGSOC.
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