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. 2023 Nov 9;28(22):7513. doi: 10.3390/molecules28227513

Table 1.

Biological effects of mitotic kinase inhibitors in TNBC cells.

Targeted
Mitotic Kinase
Cmpd Biological Effects in TNBC Models Results from Clinical Studies
on TNBC Patients or Other Tumors
In Vitro In Vivo
AURKB Barasertib (AZD1152) Reduction in mesenchymal traits [128]. Inhibition of metastatic spreading of TNBC cells in immunodeficient murine models [128]. Not available.
Adequate levels of tolerance in patients with other advanced solid tumors, with observation of stable disease [144,145].
NEK2 CMP3A Induction of mitotic alterations in synergy with PTX [124].
Induction of sensitivity to PTX in resistant cell lines [124].
Enhancing antitumoral effects of PTX in TNBC cells xenografts and PDXs [124]. Not available.
JH295 Inhibition of cells migratory and invasive properties [146]. Not available. Not available.
PLK1 Rigosertib
(ON-01910)
Reactivation of Erα expression [147]. Reduction in TNBC cell xenograft and PDX growth [147]. Not available.
Moderate toxicity in patients with other advanced solid tumors, with observation of stable disease [148,149].
Volasertib
(BI-6727)
Reactivation of Erα expression [147].
Increased DNA damage, mitotic arrest, and cell death [143,147].
Reduction in TNBC cell xenograft and PDX growth [147]. Tolerable toxicity in patients with other advanced solid tumors, either alone or in combination with other chemotherapy, with partial antitumoral effects [150,151,152,153,154].
BI-2536 Induction of mitotic abnormalities and apoptosis [125,143,155].
Reactivation of Erα expression [147].
Reduced growth of TNBC PDXs and enhanced activity towards doxorubicin and cyclophosphamide antitumoral effects [125]. Not available.
Moderate toxicity and antitumoral effects in patients with other advanced solid tumors [156].
GSK461364 Synergic antiproliferative and pro-apoptotic effects with docetaxel [157]. Not available. Not available.
Mild toxicity and moderate antitumoral effects in patients with other solid tumors [158].
Onvasertib Synergic antiproliferative and pro-apoptotic effects with docetaxel [157]. Synergic antitumoral effects with PTX in TNBC cell xenografts [157]. Not available.
One ongoing trail testing the safety and effectiveness of its combination with PTX in locally advanced and metastatic TNBC (NCT05383196).
MPS1/
TTK
CFI-402257 Inhibition of cell growth and induction of apoptosis and aneuploidy [159,160]. Antitumoral effects against TNBC cell xenografts either as a single agent or in combination with carboplatin [160]. Not available.
Three ongoing trials testing the safety and antitumoral efficacy in different BC subtypes (NCT02792465, NCT03568422, NCT05251714).
BOS172722 Induction of cell death either as stand-alone treatment or in combination with PTX [161]. Reduction in the growth of TNBC cell xenografts and PDXs and enhanced activity on the antitumoral effects of PTX [161]. Not available.
One ongoing trial testing its safety and tolerability, either alone or in combination with PTX, in advanced nonhematologic malignancies (NCT03328494).
NTRC 0066-0 Reduction in cell growth and induction of mitotic abnormalities [162]. Reduction in TNBC cell xenograft growth as a single agent. Reduction in the growth of spontaneously developing murine tumors after combination with docetaxel [162]. Not available.
BAY 1217389 Inhibition of cell growth [163]. Reduction in the growth of TNBC cell xenografts and PDXs and enhanced activity on the antitumoral effects of PTX [163]. Considerable toxicity, without a therapeutic window, in association with PTX [164].
WEE1
kinase
Adavosertib (AZD1775) Reduced cell growth both as a single agent and in association with capecitabine/5FU and/or ATR inhibitor [165,166,167]. Reduced growth of TNBC xenografts and PDXs both as a single agent and in association with capecitabine/5FU and/or ATR inhibitor [165,166,167]. Adequate levels of tolerance in TNB and other solid tumors, with stable disease in TNBC patients [168].
Not significant antitumoral effects in combination with cisplatin in metastatic TNBC [169].