Abstract
Since p53 is the strongest tumor suppressor gene, which can regulate apoptosis, cell cycle arrest and senescence, re-activation of p53 and its pathway seem to be very plausible target for cancer therapy. However, in 50% of human cancers, p53 itself is mutated. In addition, in remaining half of cancers, it is inactivated by distortion of signaling pathways. Moreover, differentially from typical tumor suppressor genes such as Rb, p53 mutations in its DNA binding domain show the dominant negative effect on p53 function. Here, we describe the novel p53 inactivation mechanism by oncogenic K-Ras-Snail axis and smart strategy to reactivation of p53 suppressed by oncogenic K-Ras-Snail through small chemicals (GN25, 29). Since K-Ras mutation is frequently occurred in human pancreatic, colon, and lung cancer, we discuss the clinical implication of new small Snail-p53 inhibitor on these cancers. In addition, the possibility of reactivation of wild type p53, governed by mutant p53, is suggested using our chemicals. Through this, we will provide the new strategy to handling the K-Ras mutated human cancers including pancreatic, lung and colon cancers.
Keywords: Oncogenic K-Ras, p53, Snail, Cancer and Therapy, MDM2, apoptosis, RITA, tumorigenesis, DN-Ras, siRNA, spiro-oxindole, oxindole, chemotherapy, GN25, GN29, adriamycin
Current Pharmaceutical Design
Title: p53 Activation by Blocking Snail : A Novel Pharmacological Strategy for Cancer
Volume: 17 Issue: 6
Author(s): Sun-Hye Lee and Bum-Joon Park
Affiliation:
Keywords: Oncogenic K-Ras, p53, Snail, Cancer and Therapy, MDM2, apoptosis, RITA, tumorigenesis, DN-Ras, siRNA, spiro-oxindole, oxindole, chemotherapy, GN25, GN29, adriamycin
Abstract: Since p53 is the strongest tumor suppressor gene, which can regulate apoptosis, cell cycle arrest and senescence, re-activation of p53 and its pathway seem to be very plausible target for cancer therapy. However, in 50% of human cancers, p53 itself is mutated. In addition, in remaining half of cancers, it is inactivated by distortion of signaling pathways. Moreover, differentially from typical tumor suppressor genes such as Rb, p53 mutations in its DNA binding domain show the dominant negative effect on p53 function. Here, we describe the novel p53 inactivation mechanism by oncogenic K-Ras-Snail axis and smart strategy to reactivation of p53 suppressed by oncogenic K-Ras-Snail through small chemicals (GN25, 29). Since K-Ras mutation is frequently occurred in human pancreatic, colon, and lung cancer, we discuss the clinical implication of new small Snail-p53 inhibitor on these cancers. In addition, the possibility of reactivation of wild type p53, governed by mutant p53, is suggested using our chemicals. Through this, we will provide the new strategy to handling the K-Ras mutated human cancers including pancreatic, lung and colon cancers.
Export Options
About this article
Cite this article as:
Lee Sun-Hye and Park Bum-Joon, p53 Activation by Blocking Snail : A Novel Pharmacological Strategy for Cancer, Current Pharmaceutical Design 2011; 17 (6) . https://dx.doi.org/10.2174/138161211795222658
DOI https://dx.doi.org/10.2174/138161211795222658 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
![](/images/wayfinder.jpg)
- 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
- Announcements
Related Articles
-
EDITORIAL(Hot Topic Integrated Therapeutic Approaches in the Treatment of Human Cancer)
Anti-Cancer Agents in Medicinal Chemistry The Management of Thymoma - A Review of the Status Quo with Practical Treatment Recommendations
Current Respiratory Medicine Reviews Dysregulated Chemokine Signaling in Cystic Fibrosis Lung Disease: A Potential Therapeutic Target
Current Drug Targets Plant Cells as Pharmaceutical Factories
Current Pharmaceutical Design Eph Receptor Tyrosine Kinases in Tumor and Tumor Microenvironment
Current Pharmaceutical Design Therapeutic Nanoparticles and Associated Toxicity
Current Nanoscience Reprofiling of Troglitazone Towards More Active and Less Toxic Derivatives: A New Hope for Cancer Treatment?
Current Topics in Medicinal Chemistry Multidrug Resistance Through the Spectacle of P-Glycoprotein
Current Cancer Drug Targets Irreversible Inhibition of Serine Proteases – Design and In Vivo Activity of Diaryl α-Aminophosphonate Derivatives
Current Medicinal Chemistry Chemoradiotherapy in Locally Advanced, Unresectable Non-Small Cell Lung Cancer
Reviews on Recent Clinical Trials The Current View on the Helicase Activity of RNA Helicase A and Its Role in Gene Expression
Current Protein & Peptide Science Precursors of Magnetic Resonance Imaging Contrast Agents Based on Cystine-coated Iron-oxide Nanoparticles
Current Physical Chemistry Lemongrass (<i>Cymbopogon citratus</i> (D.C.) Stapf) Presents Antitumoral Effect and Improves Chemotherapy Activity in Prostate Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Anticancer Metallotherapeutics in Preclinical Development
Current Medicinal Chemistry Caveolae and Caveolins in the Respiratory System
Current Molecular Medicine Autophagy : Moving Benchside Promises to Patient Bedsides
Current Cancer Drug Targets The Comparison of Pleural Fluid TNF-α and IL-10 Levels with ADA in Tuberculous Pleural Effusion
Current Medicinal Chemistry Recent Progress in Research on Ribosome Inactivating Proteins
Current Protein & Peptide Science Salivary Genomics, Transcriptomics and Proteomics: The Emerging Concept of the Oral Ecosystem and their Use in the Early Diagnosis of Cancer and other Diseases
Current Genomics Multi-Targeted Natural Products Evaluation Based on Biological Activity Prediction with PASS
Current Pharmaceutical Design