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
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
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
TNF-Related Apoptosis-Inducing Ligand (TRAIL): A Potential Candidate for Combined Treatment of Hematological Malignancies
Current Pharmaceutical Design Synthesis and <i>in Vitro</i> Cytotoxicity Evaluation of Phenanthrene Linked 2,4- Thiazolidinediones as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Angiogenesis Inhibitors: Perspectives for Medical, Surgical and Radiation Oncology
Current Pharmaceutical Design Prophylaxis of Cancer
Current Cancer Therapy Reviews COVID-19 and Autoimmune Diseases: A Systematic Review of Reported Cases
Current Rheumatology Reviews Computer-Aided Detection System for the Classification of Non-Small Cell Lung Lesions using SVM
Current Computer-Aided Drug Design Myeloma Cells and Their Interactions With the Bone Marrow Endothelial Cells
Current Immunology Reviews (Discontinued) Thymidylate Synthase Gene in Pharmacogenetics
Current Pharmacogenomics Therapeutic Exploitation of Apoptosis and Autophagy for Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in Elucidating Paclitaxel Resistance Mechanisms in Non-small Cell Lung Cancer and Strategies to Overcome Drug Resistance
Current Medicinal Chemistry The Role of Parathyroid Hormone-Related Protein (PTHrP) in the Pathophysiology of Diabetes Mellitus
Mini-Reviews in Medicinal Chemistry Detection of Squamous Cell Carcinoma Antigen with Micro- and Nanogap Interdigitated Electrodes and Gold Nanoparticles
Micro and Nanosystems miR-202 Mediates Metabolic Shift in Lung Cancer Cells via Targeting HK2
Current Signal Transduction Therapy Antiangiogenic Therapy in Malignant Glioma: Promise and Challenge
Current Pharmaceutical Design Silence of the Genes: A Targeted Approach to the Suppression of Specific Genes in Human Disease Using Small Interfering RNA (siRNA)
Current Genomics High Expression of Human Leukocyte Antigen-G is Associated with a Poor Prognosis in Patients with PDAC
Current Molecular Medicine 4-Oxothiazolidines with Exocyclic C=C Double Bond(s): Synthesis, Structure, Reactions and Biological Activity
Current Organic Chemistry Tyrosine Kinases as Therapeutic Targets in BCR-ABL Negative Chronic Myeloproliferative Disorders
Current Drug Targets Modulation of Immuno-biome during Radio-sensitization of Tumors by Glycolytic Inhibitors
Current Medicinal Chemistry Membrane Transporters as Determinants of the Pharmacology of Platinum Anticancer Drugs
Current Cancer Drug Targets