^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

PLK4 expression

i
Other names: PLK4, Polo Like Kinase 4, Serine/Threonine-Protein Kinase PLK4, Serine/Threonine-Protein Kinase Sak, Serine/Threonine-Protein Kinase 18, Polo-Like Kinase 4, STK18, SAK, Polo-Like Kinase 4 (Drosophila), Serine/Threonine Kinase 18, Snk Akin Kinase, MCCRP2, PLK-4, PLK4, Sak
Entrez ID:
5ms
Prolonged overexpression of PLK4 leads to formation of centriole rosette clusters that are connected via canonical centrosome linker proteins. (PubMed, Sci Rep)
Increased PLK4 levels in cells with C-Nap1 and Rootletin knock-out resulted with distanced CRs and CRCs in interphase, while Nek2 knock-out inhibited separation of CRCs in prometaphase, providing functional evidence for the binding of CRC structures with centrosomal linker proteins. Taken together, these results suggest a cell cycle dependent model for PLK4 induced centrosome amplification which occurs in 2 consecutive cell cycles: (i) CR state in the first cell cycle, and (ii) CRC state in the second cell cycle.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
5ms
PLK4 as a potential target to enhance radiosensitivity in triple-negative breast cancer. (PubMed, Radiat Oncol)
In our previous studies, we showed that inhibition of Polo-like Kinase 4 (PLK4) by a novel drug, CFI-400945 significantly enhances the anticancer effects of radiotherapy (RT) compared to single treatment alone...Our data suggest that PLK4 is a promising target for enhancing the anticancer effects of RT in TNBC that, at least in part, is modulated by the overamplification of centrioles. These results support further mechanistic and translational studies of anti-PLK4 agents and RT as an anticancer combination treatment strategy.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
ocifisertib (CFI-400945)
6ms
Polo-like kinase 4 promotes tumorigenesis and glucose metabolism in glioma by activating AKT1 signaling. (PubMed, Cancer Lett)
Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
6ms
Therapeutic potential of targeting polo-like kinase 4. (PubMed, Eur J Med Chem)
As such, numerous small-molecule inhibitors with distinct chemical scaffolds targeting PLK4 have been extensively investigated for the treatment of different human cancers, with several undergoing clinical evaluation (e.g., CFI-400945). Here, we review the structure, distribution, and biological functions of PLK4, encapsulate its intricate regulatory mechanisms of expression, and highlighting its multifaceted roles in cancer development and metastasis. Moreover, the recent advancements of PLK4 inhibitors in patent or literature are summarized, and their therapeutic potential as monotherapies or combination therapies with other anticancer agents are also discussed.
Review • Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
ocifisertib (CFI-400945)
7ms
Inhibition of PLK4 remodels histone methylation and activates immune response via cGAS-STING pathway in TP53 mutated AML. (PubMed, Blood)
In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53 mutated AML.
Journal • Epigenetic controller
|
TP53 (Tumor protein P53) • PLK4 (Polo Like Kinase 4)
|
TP53 mutation • TP53 wild-type • TP53 expression • PLK4 expression
8ms
HDAC Inhibitor Synergizes with GL-V9, a Derivative of Wogonin, to Suppress Acute Myeloid Leukemia By Downregulating ESPL1 and PLK4 (ASH 2023)
ConclusionOur data indicate that HDAC inhibitor Chidamide significantly synergizes GL-V9-induced cell growth inhibition, apoptosis, and cell cycle arrest in AML, and the underlying mechanism by suppressing the expression of ESPL1 and PLK4, the key regulators of cell division and proliferation. Our results also provide a potential chemotherapy-free option for AML patients.
IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • PLK4 (Polo Like Kinase 4)
|
BCL2 expression • PLK4 expression
|
Epidaza (chidamide)
9ms
Preliminary Results from a Phase 1b/2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of Cfi-400945 As a Single Agent or in Combination with Azacitidine in Patients (Pts) with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (TWT-202) (ASH 2023)
Background: CFI-400945 is a potent, selective, orally administered, first-in-class inhibitor of the serine/threonine kinase Polo-like kinase 4 (PLK4), a unique Polo-like kinase family member, that is a conserved upstream regulator of centriole duplication. CFI-400945 has been generally well tolerated in this difficult to treat patient population, including patients whose disease progressed on or following venetoclax based therapies. Three of 6 evaluable patients with AML achieved a response (MLFS=2, CRi=1) at the 96mg dose. PK characteristics support daily dosing of CFI-400945 and PD studies are ongoing.
Clinical • P1/2 data • PK/PD data • Combination therapy
|
TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • RUNX1 (RUNX Family Transcription Factor 1) • SRSF2 (Serine and arginine rich splicing factor 2) • PLK4 (Polo Like Kinase 4)
|
TP53 mutation • PLK4 expression
|
Venclexta (venetoclax) • azacitidine • ocifisertib (CFI-400945)
10ms
Polo-like Kinase 4: A Multifaceted Marker Linking Tumor Aggressiveness and Unfavorable Prognosis, and Insights into Therapeutic Strategies. (PubMed, Cancers (Basel))
PLK4 expression and pathways that were highly correlated with PLK4 expression levels were upregulated in patients with LUAD with the TP53 mutation. (4) PLK4 expression affects the survival of patients with LUAD and is a potential therapeutic target for LUAD with TP53 mutations.
Journal
|
TP53 (Tumor protein P53) • PLK4 (Polo Like Kinase 4)
|
TP53 mutation • PLK4 expression
1year
Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer. (PubMed, Int J Biol Sci)
Our findings reveal that downregulation of PLK4-induced autophagy contributes to tumor dormancy and autophagy inhibition leads to apoptosis of CRC dormant cells. Our study is the first to report that downregulation PLK4 induced autophagy is an early event in CRC dormancy and highlights autophagy inhibitor as a potential therapeutic target for dormant cell elimination.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over1year
PLK4 initiates crosstalk between cell cycle, cell proliferation and macrophages infiltration in gliomas. (PubMed, Front Oncol)
And in intracranial tumor mouse models, PLK4 inhibition increased tumor-infiltrating M1 macrophages. In summary, our results demonstrated the correlation between high PLK4 expression level and malignant progression of gliomas, and the possible involvement of PLK4 in regulation of cell cycle, cell proliferation and macrophages infiltration in gliomas.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over1year
Design, synthesis, and biological evaluation of a potent PLK4 inhibitor WY29 with 1H-pyrazolo[3,4-d]pyrimidine scaffold. (PubMed, Arch Pharm (Weinheim))
Also, the drug-like properties prediction of compound WY29 displayed remarkable drug-like properties (drug-likeness mode score: 1.06). In conclusion, these results support the further development of compound WY29 as a lead compound for PLK4-targeted anticancer drug discovery.
Journal
|
PLK1 (Polo Like Kinase 1) • PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over1year
Clinical • P2 data • PK/PD data • Combination therapy
|
TP53 (Tumor protein P53) • PLK4 (Polo Like Kinase 4)
|
TP53 mutation • PLK4 expression
|
azacitidine • decitabine • ocifisertib (CFI-400945)
almost2years
Comprehensive analysis of PLKs expression and prognosis in breast cancer. (PubMed, Cancer Genet)
For the precise therapy of breast cancers, PLK1 and PLK4 are potential targets, while PLK2, PLK3, and PLK5 are brand-new biomarkers for predicting the prognosis of breast cancer.
Review • Journal
|
PLK1 (Polo Like Kinase 1) • PLK4 (Polo Like Kinase 4) • PLK2 (Polo Like Kinase 2)
|
PLK4 expression
almost2years
PLK4 Is a Potential Biomarker for Abnormal Tumor Proliferation, Immune Infiltration, and Prognosis in ccRCC. (PubMed, Comput Math Methods Med)
Our data suggest that the PLK4 expression is closely related to the level of immune infiltration and the cytokines that exert immune suppression, and IPS was significantly higher in the PLK4 low expression group. The PLK4 expression is associated with the prognosis of ccRCC patients and affects the immune microenvironment of ccRCC, and PLK4 is expected to be a new target for the diagnosis and treatment of ccRCC.
Journal
|
PLK4 (Polo Like Kinase 4) • MIR214 (MicroRNA 214)
|
PLK4 expression
almost2years
Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines. (PubMed, Front Genet)
Consistent with above results, knockdown the expression of PLK4 also inhibited cell proliferation and colony formation, induced cell apoptosis, and caused G2/M phase cell cycle arrest without affecting cell differentiation. All in all, this study suggested that PLK4 inhibited the progression of AML in vitro, and these results herein may provide clues in roles of PLK4 in the leukemiagenesis of AML.
Preclinical • Journal • PARP Biomarker
|
CASP3 (Caspase 3) • CCNA2 (Cyclin A2) • PLK4 (Polo Like Kinase 4) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1)
|
PLK4 expression
almost2years
Polo-like Kinase 4: the Variation During Therapy and its Relation to Treatment Response and Prognostic Risk Stratification in Childhood Acute Lymphoblastic Leukemia Patients. (PubMed, J Pediatr Hematol Oncol)
Besides, PLK4 at diagnosis was positively linked with the Chinese Medical Association risk stratification (P=0.016), but not with prednisone response (P=0.077) or bone marrow response (P=0.083)...In terms of prognosis, high PLK4 was associated with shorter event-free survival (P=0.020), whereas it was not related to the overall survival (P=0.135). In conclusion, PLK4 has the potential as a biomarker for treatment response and prognostic risk stratification of childhood ALL patients.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
prednisone
2years
Polo-like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer. (PubMed, Oncol Lett)
In addition, PLK4-small interfering RNA (siRNA) was transfected into CRC cells, followed by 5-fluorouracil (5-FU) treatment for it was a fundamental chemotherapy for CRC...In conclusion, the high expression of tumor PLK4 was associated with advanced TNM stage and shorter OS in patients with CRC. In addition, targeting PLK4 improved chemosensitivity in CRC cells.
Journal
|
CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
5-fluorouracil
2years
PLK4 is upregulated in prostate cancer and its inhibition reduces centrosome amplification and causes senescence. (PubMed, Prostate)
CA is prevalent in PCa and arises predominantly by centriole overduplication as opposed to cell doubling events. Loss of centrioles is cellular stress that can promote senescence and suggests that PLK4 inhibition may be a viable therapeutic strategy in PCa.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
ocifisertib (CFI-400945)
over2years
Fraxetin down-regulates polo-like kinase 4 (PLK4) to inhibit proliferation, migration and invasion of prostate cancer cells through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. (PubMed, Bioengineered)
Finally, PLK4 overexpression significantly reversed all the effects of Fraxetin on DU145 cells. Collectively, Fraxetin acted as a cancer suppressor in prostate cancer through inhibiting PLK4 expression thereby inactivating PI3K/Akt signaling.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over2years
TEC kinase stabilizes PLK4 to promote liver cancer metastasis. (PubMed, Cancer Lett)
Further investigation by transcriptome sequencing indicated that PLK4 promotes the phosphorylation of focal adhesion kinase to regulate the focal adhesion pathway in HCC cell migration. Taken together, our results demonstrated that PLK4 plays an important role in HCC metastasis and revealed for the first time the mechanism by which PLK4 promotes HCC metastasis via TEC phosphorylation.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over2years
Hypoxia drives centrosome amplification in cancer cells via HIF-1α-dependent induction of polo-like kinase 4. (PubMed, Mol Cancer Res)
These findings suggest that HIF-1α induces CA by directly upregulating PLK4 and could help us risk-stratify patients and design new therapies for CA-rich cancers. Implications: Hypoxia drives CA in cancer cells by regulating expression of PLK4, uncovering a novel HIF-1α/ PLK4 axis.
Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • PLK4 (Polo Like Kinase 4)
|
HIF1A expression • PLK4 expression
over2years
A Phase 2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of Cfi-400945 As a Single Agent or in Combination with Azacitidine or Decitabine in Patients with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (TWT-202) (ASH 2021)
As of June 21, 2021, 2 patients had been enrolled into the study, one of the patients (50%) received >3 prior therapies (including venetoclax). CFI-400945 has been generally well tolerated and TWT-202 continues to enroll in the Part 1A and Part 1B monotherapy cohorts. Updated safety, efficacy, PK, and PD data for the study will be presented at the time of the meeting.
Clinical • P2 data • PK/PD data • Combination therapy
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
Venclexta (venetoclax) • azacitidine • decitabine • ocifisertib (CFI-400945)
over2years
Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer. (PubMed, J Pathol Transl Med)
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over2years
Targeting Polo-like Kinase 4 Triggers Polyploidy and Apoptotic Cell Death in TP53-Mutant Acute Myeloid Leukemia (ASH 2021)
While numerous novel treatment regimens, including the combination of the BCL2 inhibitor venetoclax (VEN) and hypomethylating agents (HMA), have emerged as partially effective treatments and resulted in higher remission rates in patients with TP53 -mutant AML, full clearance of the mutant TP53 clone is rarely achieved and the majority of patients relapse (Short et al., 2021; Takahashi et al., 2016). Our data suggest that TP53 -mutant AML expresses higher levels of PLK4 in comparison to TP53 -wt AML, and targeting PLK4 triggers polyploidy and apoptotic cell death in TP53 -mutant AML. A clinical trial is ongoing testing the efficacy of PLK4 inhibition (CFI-400945) in AML (Clinical Trial ID: NCT04730258, TWT-202).
IO biomarker
|
PLK4 (Polo Like Kinase 4)
|
TP53 mutation • TP53 expression • PLK4 expression
|
Venclexta (venetoclax) • ocifisertib (CFI-400945)
over2years
Clinical relevance of TRIM37 gene expression in breast cancer (SABCS 2021)
TRIM37 expression correlated with response to Cisplatin, Paclitaxel, and Tamoxifen in breast cancer cell line study (r=0.655, r=0.446, and r=0.9, respectively). Taken together, TRIM37 high expression was associated with cell proliferation regardless of subtypes, but TRIM37 low expression was associated with high tumor infiltrating lymphocytes and immune response that may have contributed to the survival difference in ER-positive/HER2-negative patients, but not in TNBC. Conclusions : In conclusion, TRIM37 expression is associated with cell proliferation and DNA repair, less tumor infiltrating lymphocytes and immune response, and with worse survival in ER-positive/HER2-negative breast cancer.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • RAD51D (RAD51 paralog D) • MKI67 (Marker of proliferation Ki-67) • PLK4 (Polo Like Kinase 4) • TRIM3 (Tripartite Motif Containing 3)
|
HER-2 positive • ER positive • HER-2 negative • HER-2 expression • ER positive + HER-2 negative • PLK4 expression
|
cisplatin • paclitaxel • tamoxifen
3years
Inhibition of Polo-like kinase 4 induces mitotic defects and DNA damage in diffuse large B-cell lymphoma. (PubMed, Cell Death Dis)
High levels of PLK4 expression were associated with poor survival in the patients receiving CHOP-based treatment, implicating PLK4 as a predictive biomarker of DLBCL chemosensitivity. These results provide the therapeutic potential of CFI-400945 both as monotherapy or in combination with doxorubicin for the treatment of DLBCL.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
doxorubicin hydrochloride • ocifisertib (CFI-400945)
over3years
CircKIF2A contributes to cell proliferation, migration, invasion and glycolysis in human neuroblastoma by regulating miR-129-5p/PLK4 axis. (PubMed, Mol Cell Biochem)
Actinomycin D assay and RNase R digestion assay were conducted to analyze the feature of circKIF2A...Additionally, circKIF2A knockdown hampered tumorigenesis in vivo. CircKIF2A knockdown suppressed cell proliferation, migration, invasion and glycolysis via downregulating PLK4 expression through miR-129-5p.
Journal
|
MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9) • PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
dactinomycin
over3years
[VIRTUAL] High expression of PLK4 as a predictor of poor prognosis for locally advanced rectal cancer patient: a prospective analysis (ECP 2020)
Conclusion Based on our human tissue study results, PLK4 expression can be suggested as a potential prognostic factor and predictor of preoperative radiotherapy resistance. Therefore, clinical development of PLK4 could be an effective therapeutic strategy for radioresistant locally advanced rectal cancer.
Clinical
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over3years
[VIRTUAL] High expression of PLK4 as a predictor of poor prognosis for locally advanced rectal cancer patient: a prospective analysis (ECP 2020)
Conclusion Based on our human tissue study results, PLK4 expression can be suggested as a potential prognostic factor and predictor of preoperative radiotherapy resistance. Therefore, clinical development of PLK4 could be an effective therapeutic strategy for radioresistant locally advanced rectal cancer.
Clinical
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over3years
[VIRTUAL] High expression of PLK4 as a predictor of poor prognosis for locally advanced rectal cancer patient: a prospective analysis (ECP 2020)
Conclusion Based on our human tissue study results, PLK4 expression can be suggested as a potential prognostic factor and predictor of preoperative radiotherapy resistance. Therefore, clinical development of PLK4 could be an effective therapeutic strategy for radioresistant locally advanced rectal cancer.
Clinical
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
over3years
[VIRTUAL] A Phase 2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of Cfi-400945 As a Single Agent or in Combination with Azacitidine or Decitabine in Patients with Acute Myeloid Leukemia (ASH 2020)
The safety endpoint is the incidence of treatment emergent adverse events. PK endpoints include evaluations of parameters such as half-life, AUC, etc. Exploratory endpoints include eval of minimal residual disease, genomic alterations and other molecular features associated with response and biological effects of PLK4 inhibition.
Clinical • P2 data • PK/PD data • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3) • PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
azacitidine • decitabine • ocifisertib (CFI-400945)
almost4years
Silencing of long non-coding RNA DLX6-AS1 weakens neuroblastoma progression by the miR-513c-5p/PLK4 axis. (PubMed, IUBMB Life)
Furthermore, the suppressive effect of miR-513c-5p overexpression on NB cell malignant progression in vitro was reversed by PLK4 upregulation. Our findings identified a novel regulatory mechanism, the DLX6-AS1/miR-513c-5p/PLK4 axis, in NB progression, highlighting a strong rationale for developing DLX6-AS1 as a new target for NB management.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
almost4years
A cis-eQTL genetic variant in PLK4 confers high risk of hepatocellular carcinoma. (PubMed, Cancer Med)
Taken together, our study demonstrated that PLK4 is a susceptibility gene and plays an oncogenic role in HCC. Furthermore, we identified that PLK4 sensitives HCC to CFI-400945, which may be an ideal therapy target for HCC.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression
|
ocifisertib (CFI-400945)
almost4years
MiR-654-3p Suppresses Non-Small Cell Lung Cancer Tumourigenesis by Inhibiting PLK4. (PubMed, Onco Targets Ther)
Finally, the animal experiment results further demonstrated that miR-654-3p inhibits tumour growth and regulates PLK4 expression. Our results demonstrate that miR-654-3p functions as a growth-suppressing miRNA by targeting PLK4 in NSCLC.
Journal
|
PLK4 (Polo Like Kinase 4)
|
PLK4 expression