Polo-like kinase inhibitors in hematologic malignancies.

Talati C; Griffiths EA; Wetzler M; Wang ES

doi:10.1016/j.critrevonc.2015.10.013

Polo-like kinase inhibitors in hematologic malignancies.

Affiliations

1. Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Authors
Talati C¹
Griffiths EA¹
Wetzler M¹
Wang ES¹
(4 authors)

ORCIDs linked to this article

Critical Reviews in Oncology/hematology, 04 Nov 2015, 98:200-210
https://doi.org/10.1016/j.critrevonc.2015.10.013 PMID: 26597019

Review

Abstract

Polo-like kinases (Plk) are key regulators of the cell cycle and multiple aspects of mitosis. Two agents that inhibit the Plk signaling pathway have shown promising activity in patients with hematologic malignancies and are currently in phase III trials. Volasertib is a Plk inhibitor under evaluation combined with low-dose cytarabine in older patients with acute myeloid leukemia (AML) ineligible for intensive induction therapy. Rigosertib, a dual inhibitor of the Plk and phosphatidylinositol 3-kinase pathways, is under investigation in patients with myelodysplastic syndrome (MDS) who have failed azacitidine or decitabine treatment. The prognosis for patients with AML, who are ineligible for intensive induction therapy, and for those with MDS refractory/relapsed after a hypomethylating agent, remains poor. Novel approaches, such as Plk inhibitors, are urgently needed for these patients. Here, we provide a comprehensive overview of the current state of development of Plk inhibitors for the treatment of hematologic malignancies.

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References

Articles referenced by this article (62)

The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus.
Andrysik Z, Bernstein WZ, Deng L, Myer DL, Li YQ, Tischfield JA, Stambrook PJ, Bahassi el M
Nucleic Acids Res, (9):2931-2943 2010
MED: 20100802
Polo-like kinases and the orchestration of cell division.
Barr FA, Sillje HH, Nigg EA
Nat Rev Mol Cell Biol, (6):429-440 2004
MED: 15173822
Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies.
Bowles DW, Diamond JR, Lam ET, Weekes CD, Astling DP, Anderson RT, Leong S, Gore L, Varella-Garcia M, Vogler BW, Keysar SB, Freas E, Aisner DL, Ren C, Tan AC, Wilhelm F, Maniar M, Eckhardt SG, Messersmith WA, Jimeno A
Clin Cancer Res, (6):1656-1665 2014
MED: 24493827
Phase I/II Study of BI 6727 (volasertib), an intravenous polo-like kinase-1 (Plk1) inhibitor, in patients with acute myeloid leukemia (AML): results of the dose finding for BI 6727 in combination with low-dose cytarabine
Bug
Blood, (21) 2010
Title not supplied
Bug
Blood, (21) 2011
Therapeutic advances in acute myeloid leukemia.
Burnett A, Wetzler M, Lowenberg B
J Clin Oncol, (5):487-494 2011
MED: 21220605
ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress.
Chapman CM, Sun X, Roschewski M, Aue G, Farooqui M, Stennett L, Gibellini F, Arthur D, Perez-Galan P, Wiestner A
Clin Cancer Res, (7):1979-1991 2012
MED: 22351695
ClinicalTrials.gov., 2014. Study of NMS-1286937 in adult patients with advanced/metastatic solid tumors. NCT01014429. <http://clinicaltrial.gov/ct2/show/NCT01014429>, (accessed 04.06.14.).
ClinicalTrials.gov., 2014. Study of orally administered TAK-960 in patients with advanced nonhematologic malignancies. NCT01179399. <http://clinicaltrials.gov/ct2/show/results/NCT01179399?term=tak-960&rank=1>, (accessed 04.06.14.).
Pretreatment prognostic factors for overall survival in primary resistant acute myeloid leukemia.
Colovic N, Tomin D, Vidovic A, Suvajdzic N, Jankovic G, Palibrk V, Djunic I, Djurasinovic V, Virijevic M
Biomed Pharmacother, (8):578-582 2011
MED: 23085253

Show 10 more references (10 of 62)

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TTK/MPS1 inhibitor OSU-13 targets the mitotic checkpoint and is a potential therapeutic strategy for myeloma.
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HMGA2 expression defines a subset of human AML with immature transcriptional signature and vulnerability to G2/M inhibition.
Moison C, Spinella JF, Chagraoui J, Lavallée VP, Lehnertz B, Thiollier C, Boivin I, Mayotte N, MacRae T, Marinier A, Hébert J, Sauvageau G
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Cited by: 6 articles | PMID: 35797243 | PMCID: PMC9631656
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
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Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.
Sorrentino VG, Thota S, Gonzalez EA, Rameshwar P, Chang VT, Etchegaray JP
Pharmaceuticals (Basel), 14(7):641, 04 Jul 2021
Cited by: 8 articles | PMID: 34358067 | PMCID: PMC8308509
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TP-0903 is active in models of drug-resistant acute myeloid leukemia.
Jeon JY, Buelow DR, Garrison DA, Niu M, Eisenmann ED, Huang KM, Zavorka Thomas ME, Weber RH, Whatcott CJ, Warner SL, Orwick SJ, Carmichael B, Stahl E, Brinton LT, Lapalombella R, Blachly JS, Hertlein E, Byrd JC, Bhatnagar B, Baker SD
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Search life-sciences literature (45,105,671 articles, preprints and more)

Polo-like kinase inhibitors in hematologic malignancies.

Affiliations

Authors

ORCIDs linked to this article

Abstract

Full text links

References

The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus.

Polo-like kinases and the orchestration of cell division.

Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies.

Phase I/II Study of BI 6727 (volasertib), an intravenous polo-like kinase-1 (Plk1) inhibitor, in patients with acute myeloid leukemia (AML): results of the dose finding for BI 6727 in combination with low-dose cytarabine

Title not supplied

Therapeutic advances in acute myeloid leukemia.

ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress.

ClinicalTrials.gov., 2014. Study of NMS-1286937 in adult patients with advanced/metastatic solid tumors. NCT01014429. <http://clinicaltrial.gov/ct2/show/NCT01014429>, (accessed 04.06.14.).

ClinicalTrials.gov., 2014. Study of orally administered TAK-960 in patients with advanced nonhematologic malignancies. NCT01179399. <http://clinicaltrials.gov/ct2/show/results/NCT01179399?term=tak-960&rank=1>, (accessed 04.06.14.).

Pretreatment prognostic factors for overall survival in primary resistant acute myeloid leukemia.

Citations & impact

Impact metrics

Citations of article over time

Alternative metrics

Article citations

TTK/MPS1 inhibitor OSU-13 targets the mitotic checkpoint and is a potential therapeutic strategy for myeloma.

Selective Wee1 Inhibitors Led to Antitumor Activity In Vitro and Correlated with Myelosuppression.

HMGA2 expression defines a subset of human AML with immature transcriptional signature and vulnerability to G2/M inhibition.

Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.

TP-0903 is active in models of drug-resistant acute myeloid leukemia.

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Funding

Boehringer Ingelheim Pharmaceuticals, Inc.

Partnerships & funding

Search life-sciences literature (45,105,671 articles, preprints and more)

Polo-like kinase inhibitors in hematologic malignancies.

Author information

Affiliations

Authors

ORCIDs linked to this article

Abstract

Full text links

References

Phase I/II Study of BI 6727 (volasertib), an intravenous polo-like kinase-1 (Plk1) inhibitor, in patients with acute myeloid leukemia (AML): results of the dose finding for BI 6727 in combination with low-dose cytarabine

Title not supplied

ClinicalTrials.gov., 2014. Study of NMS-1286937 in adult patients with advanced/metastatic solid tumors. NCT01014429. <http://clinicaltrial.gov/ct2/show/NCT01014429>, (accessed 04.06.14.).

ClinicalTrials.gov., 2014. Study of orally administered TAK-960 in patients with advanced nonhematologic malignancies. NCT01179399. <http://clinicaltrials.gov/ct2/show/results/NCT01179399?term=tak-960&rank=1>, (accessed 04.06.14.).

Citations & impact

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Citations of article over time

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Funding

Boehringer Ingelheim Pharmaceuticals, Inc.

Partnerships & funding