The potential of targeting ribosome biogenesis in high-grade serous ovarian cancer

Date

2017

Authors

Yan, Shunfei
Frank, Daniel
Son, Jinbae
Hannan, Katherine
Hannan, Ross
Chan, Keefe
Pearson, Richard B
Sanij, Elaine

Journal Title

Journal ISSN

Volume Title

Publisher

MDPI Publishing

Abstract

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 variations with 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 biogenesis has 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 olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with 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 biogenesis as a novel therapeutic approach against HGSOC.

Description

Keywords

high-grade serous carcinoma, ribosome biogenesis, Pol I, CX-5461, homologous recombination

Citation

Source

International Journal of Molecular Sciences

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

Creative Commons License (Attribution 4.0 International)

DOI

10.3390/ijms18010210

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