Abstract
Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early locoregional spread and distant metastases at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provides only modest benefit to patients with PDAC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies (monoclonal antibodies and small-molecule inhibitors) and peculiar new class of taxanes with a crucial therapeutic role in this cancer setting. A phase III trial has shown that erlotinib in combination with gemcitabine was clinically irrelevant and skin toxicity can be a positive prognostic factor. Moreover, the combination of cetuximab or erlotinib with radiotherapy in advanced pancreatic cancer has shown to be synergistic and a reversal of radio-resistance has been suggested by inhibition of VEGF/EGFR pathway. To overcome EGFR-inhibition therapy resistance several alternative pathways targets are under investigation (IGF- 1R, MMPs, Hedgehog proteins, m-TOR, MEK, COX-2) and provide the rationale for clinical use in phase II/III studies. Also nab-paclitaxel, a new taxanes class, uses high pancreatic albumin-binding protein SPARC levels to act in cancer cells with a less toxic and more effective dose with respect to classic taxanes. Understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. However, many promising data in preclinic and phase I/II trials did not yield promise in phase III trials, suggesting that identification of predictive biomarkers for these new agents is mandatory. The knowledge of biologic and molecular aspects of pancreatic cancer can be the basis for future therapeutic developments.
Keywords: bevacizumab, epidermal growth factor receptor (EGFR) inhibitors, erlotinib, hedgehog inhibitors, insuline-growth factor receptor (IGF-1R) inhibitors, metalloproteinases, nab-paclitaxel, pancreatic ductal adenocarcinoma, radiotherapy, targeted therapy, vascular endothelial growth factor (VEGF).
Current Medicinal Chemistry
Title:Target Therapies in Pancreatic Carcinoma
Volume: 21 Issue: 8
Author(s): Nicola Silvestris, Antonio Gnoni, Anna Elisabetta Brunetti, Leonardo Vincenti, Daniele Santini, Giuseppe Tonini, Francesca Merchionne, Evaristo Maiello, Vito Lorusso, Patrizia Nardulli, Amalia Azzariti and Michele Reni
Affiliation:
Keywords: bevacizumab, epidermal growth factor receptor (EGFR) inhibitors, erlotinib, hedgehog inhibitors, insuline-growth factor receptor (IGF-1R) inhibitors, metalloproteinases, nab-paclitaxel, pancreatic ductal adenocarcinoma, radiotherapy, targeted therapy, vascular endothelial growth factor (VEGF).
Abstract: Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early locoregional spread and distant metastases at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provides only modest benefit to patients with PDAC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies (monoclonal antibodies and small-molecule inhibitors) and peculiar new class of taxanes with a crucial therapeutic role in this cancer setting. A phase III trial has shown that erlotinib in combination with gemcitabine was clinically irrelevant and skin toxicity can be a positive prognostic factor. Moreover, the combination of cetuximab or erlotinib with radiotherapy in advanced pancreatic cancer has shown to be synergistic and a reversal of radio-resistance has been suggested by inhibition of VEGF/EGFR pathway. To overcome EGFR-inhibition therapy resistance several alternative pathways targets are under investigation (IGF- 1R, MMPs, Hedgehog proteins, m-TOR, MEK, COX-2) and provide the rationale for clinical use in phase II/III studies. Also nab-paclitaxel, a new taxanes class, uses high pancreatic albumin-binding protein SPARC levels to act in cancer cells with a less toxic and more effective dose with respect to classic taxanes. Understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. However, many promising data in preclinic and phase I/II trials did not yield promise in phase III trials, suggesting that identification of predictive biomarkers for these new agents is mandatory. The knowledge of biologic and molecular aspects of pancreatic cancer can be the basis for future therapeutic developments.
Export Options
About this article
Cite this article as:
Silvestris Nicola, Gnoni Antonio, Brunetti Elisabetta Anna, Vincenti Leonardo, Santini Daniele, Tonini Giuseppe, Merchionne Francesca, Maiello Evaristo, Lorusso Vito, Nardulli Patrizia, Azzariti Amalia and Reni Michele, Target Therapies in Pancreatic Carcinoma, Current Medicinal Chemistry 2014; 21 (8) . https://dx.doi.org/10.2174/09298673113209990238
DOI https://dx.doi.org/10.2174/09298673113209990238 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Imaging of Cyclooxygenase-2 (COX-2) Expression: Potential Use in Diagnosis and Drug Evaluation
Current Pharmaceutical Design AKT-pathway Inhibition in Chronic Lymphocytic Leukemia Reveals Response Relationships Defined by TCL1
Current Cancer Drug Targets Nanoscale Formulations and Diagnostics With Their Recent Trends: A Major Focus of Future Nanotechnology
Current Pharmaceutical Design Lipid Nanocarriers for Neurotherapeutics: Introduction, Challenges, Blood-brain Barrier, and Promises of Delivery Approaches
CNS & Neurological Disorders - Drug Targets Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression
MicroRNA Oncolytic Virus Therapy - Foreword
Current Cancer Drug Targets Expression of P-gp in Glioblastoma: What we can Learn from Brain Development
Current Pharmaceutical Design Oxidation Chemistry of Catecholamines and Neuronal Degeneration: An Update
Current Medicinal Chemistry Anti-diabetic Drug Metformin: Challenges and Perspectives for Cancer Therapy
Current Cancer Drug Targets Biomacromolecule-Functionalized Nanoparticle-Based Conjugates for Potentiation of Anticancer Therapy
Current Cancer Drug Targets Mechanism of Cancer Drug Resistance and the Involvement of Noncoding RNAs
Current Medicinal Chemistry Carbonic Anhydrase Inhibitors as Anticonvulsant Agents
Current Topics in Medicinal Chemistry Antiangiogenic Gene Therapy in Cancer
Current Genomics Procyanidin B2 3,3″-di-O-gallate Inhibits Endothelial Cells Growth and Motility by Targeting VEGFR2 and Integrin Signaling Pathways
Current Cancer Drug Targets Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy
Current Gene Therapy Plant Polyphenols and Tumors: From Mechanisms to Therapies, Prevention, and Protection Against Toxicity of Anti-Cancer Treatments
Current Medicinal Chemistry Current Application of Quantum Dots (QD) in Cancer Therapy: A Review
Mini-Reviews in Medicinal Chemistry Geniposide Attenuates Mitochondrial Dysfunction and Memory Deficits in APP/PS1 Transgenic Mice
Current Alzheimer Research Herbal and Traditional Chinese Medicine for the Treatment of Cardiovascular Complications in Diabetes Mellitus
Current Diabetes Reviews PDGF/PDGFR Signaling and Targeting in Cancer Growth and Progression: Focus on Tumor Microenvironment and Cancer-associated Fibroblasts
Current Pharmaceutical Design