TY - JOUR
T1 - Cyclin dependent kinase-1 (Cdk-1) inhibition as a novel therapeutic strategy against pancreatic ductal adenocarcinoma (pdac)
AU - Wijnen, Rosa
AU - Pecoraro, Camilla
AU - Carbone, Daniela
AU - Fiuji, Hamid
AU - Avan, Amir
AU - Peters, Godefridus J.
AU - Giovannetti, Elisa
AU - Diana, Patrizia
N1 - Funding Information: This work was partially supported by the following grants: CCA Foundation 2012, 2015 and 2018 grants (Godefridus J Peters, Elisa Giovannetti), KWF Dutch Cancer Society grants (KWF project#19571, #13598, Elisa Giovannetti) and AIRC IG grant 24444 (Elisa Giovannetti); PRIN2017, Prot.No.2017E84AA4 (Patrizia Diana). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - The role of CDK1 in PDAC onset and development is two-fold. Firstly, since CDK1 activity regulates the G2/M cell cycle checkpoint, overexpression of CDK1 can lead to progression into mitosis even in cells with DNA damage, a potentially tumorigenic process. Secondly, CDK1 overexpression leads to the stimulation of a range of proteins that induce stem cell properties, which can contribute to the development of cancer stem cells (CSCs). CSCs promote tumor-initiation and metastasis and play a crucial role in the development of PDAC. Targeting CDK1 showed promising results for PDAC treatment in different preclinical models, where CDK1 inhibition induced cell cycle arrest in the G2/M phase and led to induction of apoptosis. Next to this, PDAC CSCs are uniquely sensitive to CDK1 inhibition. In addition, targeting of CDK1 has shown potential for combination therapy with both ionizing radiation treatment and conventional chemotherapy, through sensitizing tumor cells and reducing resistance to these treatments. To conclude, CDK1 inhibition induces G2/M cell cycle arrest, stimulates apoptosis, and specifically targets CSCs, which makes it a promising treatment for PDAC. Screening of patients for CDK1 overexpression and further research into combination treatments is essential for optimizing this novel targeted therapy.
AB - The role of CDK1 in PDAC onset and development is two-fold. Firstly, since CDK1 activity regulates the G2/M cell cycle checkpoint, overexpression of CDK1 can lead to progression into mitosis even in cells with DNA damage, a potentially tumorigenic process. Secondly, CDK1 overexpression leads to the stimulation of a range of proteins that induce stem cell properties, which can contribute to the development of cancer stem cells (CSCs). CSCs promote tumor-initiation and metastasis and play a crucial role in the development of PDAC. Targeting CDK1 showed promising results for PDAC treatment in different preclinical models, where CDK1 inhibition induced cell cycle arrest in the G2/M phase and led to induction of apoptosis. Next to this, PDAC CSCs are uniquely sensitive to CDK1 inhibition. In addition, targeting of CDK1 has shown potential for combination therapy with both ionizing radiation treatment and conventional chemotherapy, through sensitizing tumor cells and reducing resistance to these treatments. To conclude, CDK1 inhibition induces G2/M cell cycle arrest, stimulates apoptosis, and specifically targets CSCs, which makes it a promising treatment for PDAC. Screening of patients for CDK1 overexpression and further research into combination treatments is essential for optimizing this novel targeted therapy.
KW - CDK1 inhibition
KW - Cell cycle regulation
KW - Novel treatment
KW - PDAC
KW - Pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=85113826838&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers13174389
DO - https://doi.org/10.3390/cancers13174389
M3 - Review article
C2 - 34503199
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 17
M1 - 4389
ER -