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Table 2. Ongoing trials with known inhibitory activity to centrosome aberrations
Patient
NCT number Start date Drug Targets Cancers Phases
number
NCT03654716 01 2018 ALRN-6924 MDM2 and MDMX Solid tumor 1 69
NCT03634228 08 2018 DS-3032b MDM2 Refractory Acute 2 52
Myeloid Leukemia
NCT02098967 03 2014 RO6839921 MDM2 Neoplasms, 1 68
Myelogenous Leukemia,
Acute
NCT03671564 09 2018 Milademetan MDM2 Acute Myeloid Leukemia 1 24
NCT03787602 12 2018 KRT-232 MDM2 Merkel Cell Carcinoma 2 27
NCT03781986 03 2019 APG-115 MDM2 Malignant Salivary Gland 2 62
Cancer
NCT03566485 06 2018 Atezolizumab PD-L1/MDM2 Metastatic ER + Breast 1+2 92
(an Anti-PD-L1 Cancer
Monoclonal Antibody)
With Idasanutlin
NCT01014429 11 2009 NMS-1286937 PLK1 Advanced/Metastatic 1 21
Solid Tumors
NCT01954316 10 2013 CFI-400945 PLK4 Advanced Cancer 1 48
NCT02187783 11 2014 LEE011 CDK4/6 Pathway CDK4/6 Pathway 2 106
Activated Tumors
NCT03242382 08 2017 Palbociclib CDK4 Overexpression Advanced Sarcomas 2 38
NCT00536835 09 2007 GSK461364 PLK1 Non-Hodgkins 1 40
Lymphoma
NCT03555877 06 2018 Ribociclib CDK4/6 Breast Cancer Metastatic 2 150
NCT01676753 06 2016 Dinacicli + Cyclin-dependent Kinase advanced breast cance 1 32
pembrolizumab
NCT01037790 2009 PD-0332991 CDK4 mutation Solid Tumor 2 205
NCT03242382 08 2017 Palbociclib CDK4 Overexpression Sarcoma 2 38
NCT03024489 01 2017 Palbociclib + cetuximab CDK4 Overexpression Head and Neck Cancer 2 33
NCT03310879 11 2017 Abemaciclib Abnormality in one of the Breast 2 38
following genes: CCND1,
CCND2, CCND3, CDK4,
or CDK6
NCT03050398 06 2017 Ribociclib+ letrozole CDK4/6 breast cancer 3 140
NCT03096912 06 2016 Ribociclib CDK4/6 Liposarcoma 2 30
NCT03054363 11 2017 Palbociclib + letrozole CDK4 overexpression Hormone Receptor 1 + 2 40
Positive and HER2-
positive Metastatic
Breast Cancer
NCT: National Clinical Trial

clinical trials have been setting up to a variety of human tumors, such as Leukemia, Myeloma, Brain Tumor,
Solid Tumor and Lymphoma [Table 2].

As mentioned above, PLK4 is important in centrosome biogenesis and regulates mitotic progression. PLK4
has, therefore been identified as a candidate anticancer target. With directed virtual screening using a
ligand-based focused library, several leads have been identified. CFI-400945 was generated through further
optimization . CFI-400945 is a potent and selective small molecule inhibitor of PLK4 .
[118]
[117]
Monopolar spindle 1 (Mps1/TTK) kinase is essential for safeguarding proper chromosome alignment and
segregation during mitosis . Its overexpression contributes to more aggressive and drug resistant breast
[119]
tumors but the reduction of the Mps1 level can sensitize several tumor cells to paclitaxel . In the two
[120]
ongoing clinical trials, the Mps1 inhibitors are tested along with paclitaxel in triple negative breast cancer
patients [Table 2, NCT02138812 and NCT03328494].