Yan Shunfei, Frank Daniel, Son Jinbae, Hannan Katherine M, Hannan Ross D, Chan Keefe T, Pearson Richard B, Sanij Elaine
Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
Int J Mol Sci. 2017 Jan 20;18(1):210. doi: 10.3390/ijms18010210.
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 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.
几十年来，卵巢癌（OC）患者的总生存率几乎没有改善，这意味着新的治疗选择至关重要。OC包括多种组织学亚型，其中最常见且侵袭性最强的亚型是高级别浆液性卵巢癌（HGSOC）。HGSOC的特征是基因组结构变异，相对较少发生复发性体细胞突变或可作为新型疗法开发靶点的显性致癌基因。然而，在很大比例的HGSOC中观察到控制同源重组（HR）和核糖体生物合成的信号通路失调，这增加了靶向这些基本细胞过程可能改善患者预后的可能性。聚（ADP-核糖）聚合酶（PARP）抑制剂奥拉帕尼已被批准用于治疗因种系突变而存在HR缺陷的女性。最近的证据表明，用核糖体RNA合成的特异性抑制剂CX-5461靶向核糖体生物合成，对v-myc禽髓细胞瘤病毒癌基因同源物（MYC）驱动的血液系统癌症和前列腺癌有效。CX-5461现已进入血液系统恶性肿瘤患者的I期临床试验以及乳腺癌的I/II期试验。在此，我们综述了目前可用于治疗HGSOC的靶向疗法，并讨论了靶向核糖体生物合成作为一种针对HGSOC的新型治疗方法的潜力。
