The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies

The casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic target in treatment of various human cancers. CK2 overexpression has been demonstrated in hematological malignancies, including chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acut...

Full description

Bibliographic Details
Main Authors: Hae Jung eChon, Kyoung Jun eBae, Yura eLee, Jiyeon eKim
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-03-01
Series:Frontiers in Pharmacology
Subjects:
ALL
AML
CML
CLL
CK2
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00070/full
id doaj-adc75416a5dd46afa28e273c6ae1b5dc
record_format Article
spelling doaj-adc75416a5dd46afa28e273c6ae1b5dc2020-11-24T22:29:40ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122015-03-01610.3389/fphar.2015.00070127137The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignanciesHae Jung eChon0Kyoung Jun eBae1Yura eLee2Jiyeon eKim3Eulji UniversityEulji UniversityEulji UniversityEulji UniversityThe casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic target in treatment of various human cancers. CK2 overexpression has been demonstrated in hematological malignancies, including chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and multiple myeloma. CX-4945, also known as Silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2. CX-4945 induces cytotoxicity and apoptosis and is currently being evaluated in clinical trials for treatment of many cancer types. In the past two years, the focus on the therapeutic potential of CX-4945 has shifted from solid tumors to hematological malignancies. CX-4945 exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways. Furthermore, combination of CX-4945 with other inhibitors yielded synergistic effects in cell death induction. These new findings demonstrate that CK2 overexpression contributes to blood cancer cell survival and resistance to chemotherapy. Combinatorial use of CX-4945 is a promising therapeutic tool for treatment of hematological malignancies.http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00070/fullALLAMLCMLCLLCK2CX-4945
collection DOAJ
language English
format Article
sources DOAJ
author Hae Jung eChon
Kyoung Jun eBae
Yura eLee
Jiyeon eKim
spellingShingle Hae Jung eChon
Kyoung Jun eBae
Yura eLee
Jiyeon eKim
The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies
Frontiers in Pharmacology
ALL
AML
CML
CLL
CK2
CX-4945
author_facet Hae Jung eChon
Kyoung Jun eBae
Yura eLee
Jiyeon eKim
author_sort Hae Jung eChon
title The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies
title_short The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies
title_full The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies
title_fullStr The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies
title_full_unstemmed The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies
title_sort casein kinase 2 inhibitor, cx-4945, as an anti-cancer drug in treatment of human hematological malignancies
publisher Frontiers Media S.A.
series Frontiers in Pharmacology
issn 1663-9812
publishDate 2015-03-01
description The casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic target in treatment of various human cancers. CK2 overexpression has been demonstrated in hematological malignancies, including chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and multiple myeloma. CX-4945, also known as Silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2. CX-4945 induces cytotoxicity and apoptosis and is currently being evaluated in clinical trials for treatment of many cancer types. In the past two years, the focus on the therapeutic potential of CX-4945 has shifted from solid tumors to hematological malignancies. CX-4945 exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways. Furthermore, combination of CX-4945 with other inhibitors yielded synergistic effects in cell death induction. These new findings demonstrate that CK2 overexpression contributes to blood cancer cell survival and resistance to chemotherapy. Combinatorial use of CX-4945 is a promising therapeutic tool for treatment of hematological malignancies.
topic ALL
AML
CML
CLL
CK2
CX-4945
url http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00070/full
work_keys_str_mv AT haejungechon thecaseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
AT kyoungjunebae thecaseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
AT yuraelee thecaseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
AT jiyeonekim thecaseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
AT haejungechon caseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
AT kyoungjunebae caseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
AT yuraelee caseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
AT jiyeonekim caseinkinase2inhibitorcx4945asananticancerdrugintreatmentofhumanhematologicalmalignancies
_version_ 1725743603632832512