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DRUG CLASS:

PLK1 inhibitor

14d
Single-cell landscape of innate and acquired drug resistance in acute myeloid leukemia. (PubMed, Nat Commun)
Unsupervised data integration reveals reduced ex vivo response to the Bcl-2 inhibitor venetoclax (VEN) in patients treated with both a hypomethylating agent (HMA) and VEN, compared to those pre-exposed to chemotherapy or HMA alone. Integrative analysis identifies both known and unreported mechanisms of innate and treatment-related VEN resistance and suggests alternative treatments, like targeting increased proliferation with the PLK inhibitor volasertib. Additionally, high CD36 expression in VEN-resistant blasts associates with sensitivity to CD36-targeted antibody treatment ex vivo. This study demonstrates how single-cell multi-omic profiling can uncover drug resistance mechanisms and treatment vulnerabilities, providing a valuable resource for future AML research.
Journal • IO biomarker
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CD36 (thrombospondin receptor)
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Venclexta (venetoclax) • volasertib (NBL-001)
15d
Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. (PubMed, J Clin Oncol)
Onvansertib in combination with FOLFIRI + bevacizumab showed significant activity in the second-line treatment of patients with KRAS-mutant mCRC, particularly in patients with no prior bevacizumab treatment. These findings led to the evaluation of the combination in the first-line setting (ClinicalTrails.gov identifier: NCT06106308).
P2 data • Journal • Combination therapy • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation
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Avastin (bevacizumab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • onvansertib (PCM-075)
20d
Polo-like Kinase 1 Predicts Lymph Node Metastasis in Middle Eastern Colorectal Cancer Patients; Its Inhibition Reverses 5-Fu Resistance in Colorectal Cancer Cells. (PubMed, Cells)
To investigate PLK1's role in chemoresistance, we used the specific inhibitor volasertib, which effectively reversed 5-Fu resistance...Furthermore, the knockdown of Zeb1 attenuated EMT and stemness, suggesting a possible link between EMT activation and the maintenance of stemness in CRC. Our findings underscore the pivotal role of PLK1 in mediating chemoresistance and suggest that PLK1 inhibition may represent a potential therapeutic strategy for the management of aggressive colorectal cancer subtypes.
Journal
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PLK1 (Polo Like Kinase 1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
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ZEB1 expression
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volasertib (NBL-001)
26d
USP18 promotes the proliferation, invasion, and migration of head and neck squamous cell carcinoma by deubiquitinating PLK1. (PubMed, Exp Cell Res)
Subsequently, we validated that USP18 modulated PLK1 to activate the mTORC1 pathway, thereby facilitating HNSC cell proliferation, invasion, and migration. In conclusion, our findings demonstrate that elevated expression of USP18 in HNSC cells promotes tumorigenesis by regulating the PLK1-mTORC1 pathway.
Journal
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PLK1 (Polo Like Kinase 1) • USP18 (Ubiquitin Specific Peptidase 18) • USP1 (Ubiquitin Specific Peptidase 1)
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USP18 overexpression
29d
PLK1 Inhibitor Onvansertib Enhances the Efficacy of Alpelisib in PIK3CA-Mutated HR-Positive Breast Cancer Resistant to Palbociclib and Endocrine Therapy: Preclinical Insights. (PubMed, Cancers (Basel))
Our findings support that targeting PLK1 and PI3Kα with onvansertib and alpelisib, respectively, may be a promising strategy for patients with PIK3CA-mutant HR+ breast cancer failing ET + CDK4/6i therapies and warrant clinical evaluation.
Preclinical • Journal
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PLK1 (Polo Like Kinase 1)
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HR positive • HER-2 negative • PIK3CA mutation • CDK4 mutation
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Ibrance (palbociclib) • Piqray (alpelisib) • onvansertib (PCM-075)
30d
Histone methyltransferase WHSC1 cooperate with YBX1 promote glioblastoma progression via regulating PLK1 expression. (PubMed, Cell Signal)
Furthermore, YBX1 can cooperate with WHSC1 to activate PLK1 transcription. These results shed light on the potential significance of WHSC1 in glioblastoma and offer a promising avenue for future therapeutic approaches targeting this molecule in glioblastoma treatment.
Journal • Epigenetic controller
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PLK1 (Polo Like Kinase 1) • YBX1 (Y-Box Binding Protein 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
1m
Trial suspension
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BRAF (B-raf proto-oncogene)
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BRAF mutation • BRAF V600
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Keytruda (pembrolizumab) • Estybon (rigosertib)
1m
Discovery of dual-targeted molecules based on Olaparib and Rigosertib for triple-negative breast cancer with wild-type BRCA. (PubMed, Bioorg Med Chem)
Moreover, 13b displayed superior antitumor efficacy (TGI, 61.3 %) than the single administration of Ola (TGI, 38.5 %), 11b (TGI, 51.8 %) or even their combined administration (TGI, 56.7 %), but did not show significant systematic toxicity. These findings suggest that 13b may serve as a potential candidate for BRCA wild-type TNBC.
Journal • BRCA Biomarker • PARP Biomarker
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BRCA (Breast cancer early onset)
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BRCA wild-type • BRCA mutation
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Lynparza (olaparib) • Estybon (rigosertib)
1m
NOD2 reduces the chemoresistance of melanoma by inhibiting the TYMS/PLK1 signaling axis. (PubMed, Cell Death Dis)
NOD2 inhibits thymidylate synthase (TYMS) expression by promoting K48-type ubiquitination modification of TYMS, thereby decreasing the resistance of melanoma cells to 5-fluorouracil (5-FU) and capecitabine (CAP). Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.
Journal
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TYMS (Thymidylate Synthetase) • PLK1 (Polo Like Kinase 1) • NLRC5 (NLR Family CARD Domain Containing 5)
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TYMS expression
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5-fluorouracil • capecitabine • volasertib (NBL-001)
2ms
HN1 expression contributes to mitotic fidelity through Aurora A-PLK1-Eg5 axis. (PubMed, Cytoskeleton (Hoboken))
Further, the PLK1 and Aurora A kinase's phosphorylations also decreased, confirming the hypothesis that the cells struggle in mitotic progression, display nuclear and cytokinetic abnormalities with supernumerary but immature mononucleated centrosomes. In summary, we described the role of HN1 in centrosome nucleation/maturation in PLK1-Eg5 axis and concomitant mitotic spindle formation in human cells.
Journal
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CDH1 (Cadherin 1) • AURKA (Aurora kinase A) • PLK1 (Polo Like Kinase 1) • PCM1 (Pericentriolar Material 1) • CCNB1 (Cyclin B1) • JPT1 (Jupiter Microtubule Associated Homolog 1)
2ms
Biomimetic Nanosensitizer Potentiates Efficient Glioblastoma Gene-Radiotherapy through Synergistic Hypoxia Mitigation and PLK1 Silencing. (PubMed, ACS Appl Mater Interfaces)
By enabling prolonged miRNA circulation in the bloodstream and achieving high enrichment at the tumor site, CNL@miPA significantly suppressed tumor growth in combination treatment, thereby significantly extending the survival period of treated mice. Overall, the developed biomimetic nanosensitizer represented an efficient and multifunctional targeted delivery system, offering a novel strategy for gene-radiotherapy of GBM.
Journal
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PLK1 (Polo Like Kinase 1)
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PLK1 overexpression
2ms
A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS (clinicaltrials.gov)
P1, N=7, Terminated, Cyclacel Pharmaceuticals, Inc. | N=50 --> 7 | Recruiting --> Terminated; Switch to oral formulation of CYC140 (plogosertib)
Enrollment change • Trial termination • Metastases
2ms
Journal
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KRAS (KRAS proto-oncogene GTPase) • PLK1 (Polo Like Kinase 1)
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KRAS mutation
2ms
Integrating network analysis with differential expression to uncover therapeutic and prognostic biomarkers in esophageal squamous cell carcinoma. (PubMed, Front Mol Biosci)
We also identify the molecules targeting these essential hub genes, among which GSK461364 is a promising inhibitor of PLK1, BMS265246, and Valrubicin inhibitors of CDK1 and TOP2A, respectively. Notably, MMP9 emerged as a significant prognostic marker with high expression correlating with poor survival, underscoring its potential for targeted therapy. These findings enhance our understanding of ESCC pathogenesis and highlight promising avenues for treatment.
Journal
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TOP2A (DNA topoisomerase 2-alpha) • PLK1 (Polo Like Kinase 1) • MMP9 (Matrix metallopeptidase 9) • CDK1 (Cyclin-dependent kinase 1) • MAD2L1 (Mitotic Arrest Deficient 2 Like 1)
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MMP9 elevation • TOP2A expression
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GSK461364 • valrubicin
2ms
Therapeutic Potential of PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1 Genes in Triple-Negative Breast Cancer: Correlating Their Expression with Sensitivity to GSK 461364 and IKK 16 Drugs. (PubMed, Biochem Genet)
The results of this study showed a significant increase in the expression level of PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1 in TNBC compared to other BC subgroups. These genes show considerable promise as therapeutic targets for the TNBC subgroup.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PLK1 (Polo Like Kinase 1) • AURKB (Aurora Kinase B) • PTTG1 (PTTG1 Regulator Of Sister Chromatid Separation, Securin) • CDT1 (Chromatin Licensing And DNA Replication Factor 1) • KIF4A (Kinesin Family Member 4A) • UBE2C (Ubiquitin Conjugating Enzyme E2 C)
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GSK461364
3ms
Regulated induced proximity targeting chimeras-RIPTACs-A heterobifunctional small molecule strategy for cancer selective therapies. (PubMed, Cell Chem Biol)
In this chemical biology study, we design RIPTACs that incorporate a ligand against a model TP connected via a linker to effector ligands such as JQ1 (BRD4) or BI2536 (PLK1) or CDK inhibitors such as TMX3013 or dinaciclib. RIPTACs accumulate selectively in cells expressing the HaloTag-FKBP target, form co-operative intracellular ternary complexes, and induce an anti-proliferative response in target-expressing cells.
Journal
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PLK1 (Polo Like Kinase 1) • BRD4 (Bromodomain Containing 4)
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JQ-1 • dinaciclib (MK-7965) • BI2536
3ms
Affinity enhancement of polo-like kinase 1 polo box domain-binding ligands by a bivalent approach using a covalent kinase-binding component. (PubMed, RSC Chem Biol)
We found that bivalent ligands incorporating Wortmannin demonstrated affinity enhancements that could be similar to what we had obtained with BI2536 and that they could tightly bind to the protein. This suggests that these tight binding ligands might be useful for structural analysis of full-length Plk1.
Journal
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PLK1 (Polo Like Kinase 1)
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BI2536
4ms
BRCA1 orchestrates the response to BI-2536 and its combination with alisertib in MYC-driven small cell lung cancer. (PubMed, Cell Death Dis)
Our findings indicate that the BRCA1 and MYC/MYCN-RAD51 axes govern the response of small cell lung cancer to BI-2536 and its combination with alisertib. This study propose the combined use of BI-2536 and alisertib as a novel therapeutic strategy for the treatment of SCLC patients with MYC/MYCN activation.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • RAD51 (RAD51 Homolog A) • AURKA (Aurora kinase A)
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alisertib (MLN8237) • BI2536
4ms
The construction of a prognostic model by apoptosis-related genes to predict survival, immune landscape, and medication in cholangiocarcinoma. (PubMed, Clin Res Hepatol Gastroenterol)
Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients.
Journal
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MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
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Estybon (rigosertib) • AMG 900
4ms
Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas. (PubMed, Cell Death Dis)
We could demonstrate that in vitro onvansertib inhibited both HR and non-homologous end-joining repair pathways and in vivo induced a decrease in the number of RAD51 foci-positive tumor cells, supporting its ability to induce HR deficiency and favoring the activity of olaparib. Considering that the combination was well tolerated, these data support and foster the clinical evaluation of onvansertib with PARPis in ovarian cancer, particularly in the PARPis-resistant setting.
Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • RAD51 (RAD51 Homolog A)
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Lynparza (olaparib) • onvansertib (PCM-075)
4ms
Enrollment change • Trial withdrawal • Combination therapy • Metastases
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gemcitabine • albumin-bound paclitaxel • onvansertib (PCM-075)
4ms
Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling. (PubMed, Cell Rep Med)
Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • PLK1 (Polo Like Kinase 1)
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Xospata (gilteritinib) • metformin
4ms
Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton. (PubMed, Cell Rep)
Expression of a non-degradable AKAP2 mutant resulted in actin defects and aberrant mitotic spindles, suggesting that AKAP2 degradation coordinates cytoskeletal organization during mitosis. These findings uncover PLK1's far-reaching role in shaping the mitotic proteome post-translationally and have potential implications in malignancies where PLK1 is upregulated.
Journal
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PLK1 (Polo Like Kinase 1) • CUL1 (Cullin 1) • CCNF (Cyclin F)
4ms
Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis. (PubMed, Cell Rep)
Collectively, the results support that PLK1-phosphorylated BRD4 triggers its degradation at M phase. Sequential treatment of docetaxel and JQ1 overcomes BRD4 accumulation-associated bromodomain and extra-terminal inhibitor (BETi) resistance, which may shed light on the development of strategies to treat PCa.
Journal
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PLK1 (Polo Like Kinase 1) • SPOP (Speckle Type BTB/POZ Protein) • BRD4 (Bromodomain Containing 4) • CDK1 (Cyclin-dependent kinase 1)
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docetaxel • JQ-1
4ms
BAL0891 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=216, Recruiting, SillaJen, Inc. | N=120 --> 216
Enrollment change • Combination therapy • Metastases
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carboplatin • paclitaxel • BAL0891
5ms
Auranofin and reactive oxygen species inhibit protein synthesis and regulate the level of the PLK1 protein in Ewing sarcoma cells. (PubMed, Front Oncol)
In particular, we identified that both hydrogen peroxide and auranofin, an inhibitor of thioredoxin reductase and regulator of oxidative stress and reactive oxygen species, activate the repressor of protein translation 4E-BP1 and reduce the levels of the oncogenic proteins RRM2 and PLK1 in Ewing and other sarcoma cell lines. These results provide novel insight into the mechanism of how ROS-inducing drugs target cancer cells via inhibition of protein translation and identify a mechanistic link between ROS and the DNA replication (RRM2) and cell cycle regulatory (PLK1) pathways.
Journal
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PLK1 (Polo Like Kinase 1) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2)
5ms
MYC and HSF1 Cooperate to Drive PLK1 inhibitor Sensitivity in High Grade Serous Ovarian Cancer. (PubMed, bioRxiv)
Targeting PLK1 with the compound volasertib (BI-6727) revealed a greater than 200-fold increased potency of volasertib in HSF1-MYC co-amplified ovarian cancer cells compared to ovarian cancer cells wild-type HSF1 and MYC copy number, which extended to several growth assays, including spheroid growth. Volasertib, and other PLK1 inhibitors, have not shown great success in clinical trials and this study suggests that targeting PLK1 may be viable in a precision medicine approach using HSF1-MYC co-amplification as a biomarker for response.
Journal
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HSF1 (Heat Shock Transcription Factor 1)
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volasertib (NBL-001)
5ms
Resistance to Spindle Inhibitors in Glioblastoma Depends on STAT3 and Therapy Induced Senescence. (PubMed, bioRxiv)
Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. These results support a therapeutic strategy of targeting STAT3-dependent therapy-induced senescence to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma. • Resistance to non-microtubule spindle inhibitors limits their efficacy in glioblastoma and depends on STAT3.• Resistance goes hand in hand with development of therapy induced senescence (TIS).• Spindle inhibitor resistant glioblastomas consist of three cell subpopulations-proliferative, quiescent, and TIS-with proliferative cells sensitive and quiescent and TIS cells resistant.• TIS cells secrete TGFβ, which induces proliferative cells to become quiescent, thereby expanding the population of resistant cells in a spindle inhibitor resistant glioblastoma• Treatment with a STAT3 inhibitor kills TIS cells and restores sensitivity to spindle inhibitors.
Journal
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STAT3 (Signal Transducer And Activator Of Transcription 3) • TGFB1 (Transforming Growth Factor Beta 1)
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volasertib (NBL-001) • alisertib (MLN8237) • ispinesib (SB-715992)
5ms
AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer. (PubMed, Mol Cancer Ther)
We initially confirmed that the PLK1 specific inhibitor onvansertib (ONV) could enhance responses to a PARP inhibitor (olaparib) in prostate cancer xenografts...We confirmed in vitro synergy between ONV and the AKT inhibitor ipatasertib (IPA) and found that the combination increased apoptosis...Studies in three PTEN deficient prostate cancer xenograft models showed that co-treatment with IPA and ONV led to significant tumor growth inhibition compared to monotherapies. Together these in vitro and in vivo studies demonstrate that the efficacy of PLK1 antagonists can be enhanced by PARP or AKT inhibition, and support further development of these combination therapies.
Journal • PARP Biomarker
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PTEN (Phosphatase and tensin homolog) • BIRC5 (Baculoviral IAP repeat containing 5) • PLK1 (Polo Like Kinase 1)
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Lynparza (olaparib) • ipatasertib (RG7440) • onvansertib (PCM-075)
5ms
A miR-361-5p/ ORC6/ PLK1 axis regulates prostate cancer progression. (PubMed, Exp Cell Res)
PLK1 overexpression or miR-361-5p inhibitor treatment effectively removed the inhibitory effects caused by ORC6 silencing. Notably, our data showed that therapeutically targeting the miR-361-5p/ ORC6/ PLK1 axis may be a viable therapy option for PCa.
Journal
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PLK1 (Polo Like Kinase 1) • MIR361 (MicroRNA 361) • E2F1 (E2F transcription factor 1)
5ms
Single-cell analysis identifies PLK1 as a driver of immunosuppressive tumor microenvironment in LUAD. (PubMed, PLoS Genet)
Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.
Journal • IO biomarker
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PLK1 (Polo Like Kinase 1)
6ms
PI3K inhibitor idelalisib enhances the anti-tumor effects of CDK4/6 inhibitor palbociclib via PLK1 in B-cell lymphoma. (PubMed, Cancer Lett)
Furthermore, we also validated the pharmacological efficacy of CDK4/6 inhibitor palbociclib and its synergy effect with PI3K inhibitor idelalisib utilizing in vitro cell lines and in vivo cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Our results provided sufficient pre-clinical evidence to support the potential combination of palbociclib and idelalisib for DLBCL and MCL patients.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PLK1 (Polo Like Kinase 1)
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Ibrance (palbociclib) • Zydelig (idelalisib)
6ms
PLK1 inhibition leads to mitotic arrest and triggers apoptosis in cholangiocarcinoma cells. (PubMed, Oncol Lett)
Different CCA cell lines developed from Thai patients, HuCCA1, KKU055, KKU100 and KKU213A, were treated with two PLK1 inhibitors, BI2536 and BI6727, and were transfected with small interfering RNA, followed by analysis of cell proliferation, cell cycle distribution and cell apoptosis. Validation of the antiproliferative effects of PLK1 inhibition was accomplished through silencing of the PLK1 gene. In conclusion, targeting PLK1 provided promising results for further study as a potential candidate for targeted therapy in CCA.
Journal
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AURKA (Aurora kinase A) • CCNB1 (Cyclin B1)
|
volasertib (NBL-001) • BI2536
6ms
Thinking Outside the Box: Indirect Myc Modulation in Canine B-Cell Lymphoma. (PubMed, Animals (Basel))
Furthermore, BI2536, both alone and in combination with MZ1, induced larger transcriptomic changes in cells compared to MZ1 alone, primarily affecting MYC target genes and genes involved in cell cycle regulation. These data underscore the potential role of Myc as therapeutic target in cBCL, providing a novel approach to indirectly modulate this molecule.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PLK1 (Polo Like Kinase 1) • BRD4 (Bromodomain Containing 4)
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BI2536
6ms
Overexpression of PLK1 Molecule Following Incomplete Thermal Ablation Promotes the Proliferation and Invasion of Residual Hepatocellular Carcinoma. (PubMed, Mol Biotechnol)
Meanwhile, PLK1 has different regulatory effects on various EMT pathway proteins. PLK1 promotes the progression of residual HCC by activating EMT pathway after ITA, which might provide a novel idea for the treatment and prognosis of residual HCC.
Journal
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PLK1 (Polo Like Kinase 1)
6ms
Targeted PLK1 suppression through RNA interference mediated by high-fidelity Cas13d mitigates osteosarcoma progression via TGF-β/Smad3 signalling. (PubMed, J Cell Mol Med)
It also demonstrates the utility of hfCas13d-mediated gene knockdown as a strategy for targeted therapy. Further optimization of PLK1 suppression approaches may ultimately improve clinical outcomes for osteosarcoma patients.
Journal
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CDH1 (Cadherin 1) • PLK1 (Polo Like Kinase 1) • TGFB1 (Transforming Growth Factor Beta 1) • SMAD3 (SMAD Family Member 3)
6ms
Therapeutic targeting of PLK1 in TERT promoter-mutant hepatocellular carcinoma. (PubMed, Clin Transl Med)
TERT promoter mutation confers sensitivity to PLK1 inhibitors in HCC. The selective growth inhibition of TERT mutant HCC cells induced by PLK1 inhibitor was mediated by Smad3. Combined inhibition of PLK1 and Smad3 showed a cooperative anti-tumor effect in TERT mutant HCC cells.
Journal
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TERT (Telomerase Reverse Transcriptase) • PLK1 (Polo Like Kinase 1) • ANXA5 (Annexin A5) • SMAD3 (SMAD Family Member 3)
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TERT mutation • TERT promoter mutation
6ms
Phosphorylation of LZTS2 by PLK1 activates the Wnt pathway. (PubMed, Cell Signal)
Finally, PLK1 inhibitors exhibit a dose-dependent suppression of LUAD cell proliferation and migration. Collectively, this study uncovers the pro-tumorigenic mechanism of PLK1, positioning it as a promising therapeutic target for Wnt-related LUAD.
Journal
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PLK1 (Polo Like Kinase 1)
6ms
Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment (clinicaltrials.gov)
P1/2, N=25, Completed, Icahn School of Medicine at Mount Sinai | Recruiting --> Completed
Trial completion • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation
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Opdivo (nivolumab) • Estybon (rigosertib)
6ms
Mitotic Kinases Aurora-A, Plk1, and Cdk1 Interact with Elk-1 Transcription Factor through the N-Terminal Domain. (PubMed, Int J Cell Biol)
We also perform bioinformatic analysis of mitotic phosphoproteomes and determine potential interaction partners for Elk-1 in Plk or Aurora phosphoproteomes. We propose that understanding the dynamic phosphorylation of Elk-1 by mitotic kinases is important and that it can present a novel target for anticancer strategies.
Journal
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PLK1 (Polo Like Kinase 1) • CDK1 (Cyclin-dependent kinase 1)