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Ref Type Journal Article
PMID (32183025)
Authors Affatato R, Carrassa L, Chilà R, Lupi M, Restelli V, Damia G
Title Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma.
Journal Vol Issue Date Pages Journal Short Title
Cancers 12 3 2020 Mar 13 Cancers (Basel)
URL
Abstract Text Mucinous epithelial ovarian cancer (mEOC) is a rare subset of epithelial ovarian cancer. When diagnosed at a late stage, its prognosis is very poor, as it is quite chemo-resistant. To find new therapeutic options for mEOC, we performed high-throughput screening using a siRNA library directed against human protein kinases in a mEOC cell line, and polo-like kinase1 (PLK1) was identified as the kinase whose downregulation interfered with cell proliferation. Both PLK1 siRNA and two specific PLK1 inhibitors (onvansertib and volasertib) were able to inhibit cell growth, induce apoptosis and block cells in the G2/M phase of the cell cycle. We evaluated, in vitro, the combinations of PLK1 inhibitors and different chemotherapeutic drugs currently used in the treatment of mEOC, and we observed a synergistic effect of PLK1 inhibitors and antimitotic drugs. When translated into an in vivo xenograft model, the combination of onvansertib and paclitaxel resulted in stronger tumor regressions and in a longer mice survival than the single treatments. These effects were associated with a higher induction of mitotic block and induction of apoptosis, similarly to what was observed in vitro. These data suggest that the combination onvansertib/paclitaxel could represent a new active therapeutic option in mEOC.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Onvansertib Onvansertib 0 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
Onvansertib PCM-075|PCM 075|NMS-P937 PLK1 Inhibitor 18 Onvansertib (PCM-075) is an ATP-competitive inhibitor of PLK1, which may result in cell cycle arrest, apoptosis, reduced tumor cell proliferation and colony formation in culture, and decreased tumor formation in mouse models (PMID: 22319201, PMID: 32017934, PMID: 32183025).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References