Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and devastating disease, which is characterized by invasiveness and dissemination to the lymphatic system and distant organs. In the absence of effective screening methods considerable efforts have thus been made to identify better systemic treatments than gemcitabine, the standard of care for advanced PDAC for well over a decade. However, until now only erlotinib, an epidermal growth-factor receptor tyrosine kinase inhibitor, has demonstrated a modest survival benefit in combination with gemcitabine in a phase III clinical trial. More recently, detailed global genomic analyses have provided a snapshot of the landscape of tumor genomes by showing that they contain four high frequency mutated genes and many low frequency mutated genes that correspond to 12 core signaling pathways. Strategies to target these frequently altered genes and their pathways, or low frequency mutated genes corresponding to the “personalized genome”, offer novel therapeutic strategies. In the near future, the complete sequencing of the coding genome, together with the dramatically reduced costs of whole genome sequencing, will provide new opportunities to treat PDAC.
Keywords: Whole genome sequencing, KRAS, TP53, CDKN2A/p16, SMAD4/DPC4, hedgehog pathway, personalized genome
Current Pharmaceutical Design
Title:Novel Therapeutic Approaches in Pancreatic Cancer Based on Genomic Alterations
Volume: 18 Issue: 17
Author(s): Shinichi Yachida
Affiliation:
Keywords: Whole genome sequencing, KRAS, TP53, CDKN2A/p16, SMAD4/DPC4, hedgehog pathway, personalized genome
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and devastating disease, which is characterized by invasiveness and dissemination to the lymphatic system and distant organs. In the absence of effective screening methods considerable efforts have thus been made to identify better systemic treatments than gemcitabine, the standard of care for advanced PDAC for well over a decade. However, until now only erlotinib, an epidermal growth-factor receptor tyrosine kinase inhibitor, has demonstrated a modest survival benefit in combination with gemcitabine in a phase III clinical trial. More recently, detailed global genomic analyses have provided a snapshot of the landscape of tumor genomes by showing that they contain four high frequency mutated genes and many low frequency mutated genes that correspond to 12 core signaling pathways. Strategies to target these frequently altered genes and their pathways, or low frequency mutated genes corresponding to the “personalized genome”, offer novel therapeutic strategies. In the near future, the complete sequencing of the coding genome, together with the dramatically reduced costs of whole genome sequencing, will provide new opportunities to treat PDAC.
Export Options
About this article
Cite this article as:
Yachida Shinichi, Novel Therapeutic Approaches in Pancreatic Cancer Based on Genomic Alterations, Current Pharmaceutical Design 2012; 18 (17) . https://dx.doi.org/10.2174/13816128112092452
DOI https://dx.doi.org/10.2174/13816128112092452 |
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
-
Signal Transduction Targets in Prostate Cancer
Current Signal Transduction Therapy Novel Rational Drug Design Strategies with Potential to Revolutionize Malaria Chemotherapy
Current Medicinal Chemistry Therapeutic Gene Products Delivery by Neuron Stem Cells
Current Pharmaceutical Biotechnology Mango Polyphenols and Its Protective Effects on Diseases Associated to Oxidative Stress
Current Pharmaceutical Biotechnology Pattern of Care for Skin Cancers - Canada and France
Current Cancer Therapy Reviews Connection between JAK/STAT and PPARγ Signaling During the Progression of Multiple Sclerosis: Insights into the Modulation of T-Cells and Immune Responses in the Brain
Current Molecular Pharmacology GLUT4 Goes Abnormal: Disregulation of the Insulin-Responsive Glucose Transporter in Abnormal Metabolic States
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Phytochemical and Biological Activities of an Anticancer Plant Medicine: Brucea javanica
Anti-Cancer Agents in Medicinal Chemistry Twist-BRD4 Complex: Potential Drug Target for Basal-like Breast Cancer
Current Pharmaceutical Design New Avenue of Research: Antiepileptic Drug and Estradiol Neuroprotection in Epilepsy
Recent Patents on CNS Drug Discovery (Discontinued) Targeting ErbB Receptors in High-Grade Glioma
Current Pharmaceutical Design Sunitinib in the Treatment of Thyroid Cancer
Current Medicinal Chemistry Formulation, Characterization and In vitro Cytotoxicity of 5-Fluorouracil Loaded Polymeric Electrospun Nanofibers for the Treatment of Skin Cancer
Recent Patents on Nanotechnology Development of Anti-Atherosclerosis Therapy Based on the Inflammatory and Proliferative Aspects of the Disease
Current Pharmaceutical Design Cardiomyocyte-Specific TβR2 Knockout Mice are More Susceptible to Cardiac Hypertrophy Induced by Adrenergic Agonist Stimulation
Current Molecular Medicine Role of Translocator Protein in Renal Ischemia Reperfusion, Renal Preservation and Acute Kidney Injury
Current Molecular Medicine Tumor-Receptor Imaging in Breast Cancer: A Tool for Patient Selection and Response Monitoring
Current Molecular Medicine Reversal of Resistance to Oxazaphosphorines
Current Cancer Drug Targets Emerging Role of Stromal Fibroblasts in Epithelial Cancer
Current Signal Transduction Therapy T-Cell Zeta Chain Expression, Phosphorylation and Degradation and their Role in T-Cell Signal Transduction and Immune Response Regulation in Health And Disease
Current Signal Transduction Therapy