The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

被引：22
作者：
Yan, Shunfei [1 ,2 ]
Frank, Daniel [1 ,3 ]
Son, Jinbae [1 ,2 ]
Hannan, Katherine M. [3 ,4 ]
Hannan, Ross D. [1 ,2 ,3 ,4 ,5 ,6 ]
Chan, Keefe T. [1 ]
Pearson, Richard B. [1 ,2 ,3 ,5 ]
Sanij, Elaine [1 ,7 ]
机构：
[1] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic 3000, Australia
[2] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia
[3] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia
[4] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia
[5] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3168, Australia
[6] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia
[7] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2017年 / 18卷 / 01期
基金：
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词：
high-grade serous carcinoma; ribosome biogenesis; Pol I; CX-5461; homologous recombination; RNA-POLYMERASE-I; HOMOLOGOUS RECOMBINATION DEFICIENCY; OLAPARIB MAINTENANCE THERAPY; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADVANCED SOLID TUMORS; C-MYC; CELL-GROWTH; GRANULOCYTE DIFFERENTIATION; CISPLATIN RESISTANCE; PLATINUM RESISTANCE;
D O I：
10.3390/ijms18010210
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
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页数：17
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