Abstract
p21CDKN1A (WAF1/CIP1/SDI1), the cyclin-dependent kinase (CDK) inhibitor belonging to the Cip/Kip family, was first described as a potent inhibitor of cell proliferation and DNA replication, both in physiological conditions and after DNA damage. More recently, p21 has been recognized to play additional and fundamental roles in other important pathways, including regulation of transcription, apoptosis and DNA repair. Knock-out mouse studies combined with biochemical and functional analysis of cells in culture have indicated a tumor suppressor activity for p21. However, these lines of evidence have been complicated by other findings indicating that p21 can exhibit oncogenic properties. In fact, the evidence that p21 expression may lead to proliferation arrest, is counterbalanced by the rescue of tumor cells from drug-induced apoptosis, and by promoting a metastatic potential. For these reasons, p21 is considered a protein with a dual behavior, with potential benefits, as well as dangerous effects of its expression in malignant cells. Thus, the effectiveness of targeting p21 expression for antitumor therapy needs to be carefully evaluated accordingly. This review summarizes the functions and regulations of p21, and focuses on its involvement in human diseases (particularly cancer), and on the pharmacological approaches to target p21 expression (either positively or negatively) for anticancer therapy. Based on these approaches, the search for new molecules that are able to promote the tumor-suppressor activity, and/or to interfere with the oncogenic properties of p21, could be promising.
Keywords: Anti-cancer target, CDK inhibitor, cell cycle regulator, p21CDKN1A, Apoptosis signal-regulating kinase 1, Base excision repair, Histone Deacetylase, Melanoma differentiation-associated protein 6, Mouse mammary tumor virus, Nucleotide excision repair, Nuclear localization signal, Transcription factor, Wild type p53-activated fragment 1, Translesion DNA synthesis
Current Cancer Drug Targets
Title: The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs
Volume: 12 Issue: 2
Author(s): L. A. Stivala, O. Cazzalini and E. Prosperi
Affiliation:
Keywords: Anti-cancer target, CDK inhibitor, cell cycle regulator, p21CDKN1A, Apoptosis signal-regulating kinase 1, Base excision repair, Histone Deacetylase, Melanoma differentiation-associated protein 6, Mouse mammary tumor virus, Nucleotide excision repair, Nuclear localization signal, Transcription factor, Wild type p53-activated fragment 1, Translesion DNA synthesis
Abstract: p21CDKN1A (WAF1/CIP1/SDI1), the cyclin-dependent kinase (CDK) inhibitor belonging to the Cip/Kip family, was first described as a potent inhibitor of cell proliferation and DNA replication, both in physiological conditions and after DNA damage. More recently, p21 has been recognized to play additional and fundamental roles in other important pathways, including regulation of transcription, apoptosis and DNA repair. Knock-out mouse studies combined with biochemical and functional analysis of cells in culture have indicated a tumor suppressor activity for p21. However, these lines of evidence have been complicated by other findings indicating that p21 can exhibit oncogenic properties. In fact, the evidence that p21 expression may lead to proliferation arrest, is counterbalanced by the rescue of tumor cells from drug-induced apoptosis, and by promoting a metastatic potential. For these reasons, p21 is considered a protein with a dual behavior, with potential benefits, as well as dangerous effects of its expression in malignant cells. Thus, the effectiveness of targeting p21 expression for antitumor therapy needs to be carefully evaluated accordingly. This review summarizes the functions and regulations of p21, and focuses on its involvement in human diseases (particularly cancer), and on the pharmacological approaches to target p21 expression (either positively or negatively) for anticancer therapy. Based on these approaches, the search for new molecules that are able to promote the tumor-suppressor activity, and/or to interfere with the oncogenic properties of p21, could be promising.
Export Options
About this article
Cite this article as:
A. Stivala L., Cazzalini O. and Prosperi E., The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs, Current Cancer Drug Targets 2012; 12 (2) . https://dx.doi.org/10.2174/156800912799095126
DOI https://dx.doi.org/10.2174/156800912799095126 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Classical Inhibitors of NOX NAD(P)H Oxidases Are Not Specific
Current Drug Metabolism Epigenetic Variation and Customising Nutritional Intervention
Current Pharmacogenomics and Personalized Medicine Engineered Biosynthesis of Medicinally Important Plant Natural Products in Microorganisms
Current Topics in Medicinal Chemistry Targeted Radionuclide Therapy of Painful Bone Metastases: Past Developments, Current Status, Recent Advances and Future Directions
Current Medicinal Chemistry Current Phthalocyanines Delivery Systems in Photodynamic Therapy: An Updated Review
Current Medicinal Chemistry Biotransformation of Silybin and its Congeners
Current Drug Metabolism In Situ Gene Therapy for Prostate Cancer
Current Gene Therapy Ligands and Therapeutic Perspectives of Adenosine A2A Receptors
Current Pharmaceutical Design Histone Deacetylase Inhibitors: The Abbott Experience
Current Medicinal Chemistry Photothermal Ablation of Cancer Cells Using Folate-Coated Gold/ Graphene Oxide Composite
Current Drug Delivery Transmission Electron Microscopy as Key Technique for the Characterization of Telocytes
Current Stem Cell Research & Therapy Physicochemical Properties that Determine Cellular Transport of Nanocarriers In Vitro and In Vivo
Current Organic Chemistry Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases
Current Genomics Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy
Current Cancer Drug Targets Cationic Liposome Mediated Delivery of FUS1 and hIL-12 Coexpression Plasmid Demonstrates Enhanced Activity against Human Lung Cancer
Current Cancer Drug Targets Epigenetic Mechanism Involved in the HBV/HCV-Related Hepatocellular Carcinoma Tumorigenesis
Current Pharmaceutical Design Biological Modulation by Lectins and Their Ligands in Tumor Progression and Metastasis
Anti-Cancer Agents in Medicinal Chemistry Specific Targeting of Akt Kinase Isoforms: Taking the Precise Path for Prevention and Treatment of Cancer
Current Drug Targets The Rapidly Changing Composition of the Global Street Drug Supply and its Effects on High-risk Groups for COVID-19
Current Psychopharmacology Prediction of the Ebola Virus Infection Related Human Genes Using Protein-Protein Interaction Network
Combinatorial Chemistry & High Throughput Screening