Abstract
Gastric cancer represents one of the most common cancer worldwide. Unfortunately, the majority of patients present in advanced stage and outcome still remains poor with high mortality rate despite decreasing incidence and new diagnostic and therapeutic strategies. Although utility of classical chemotherapy agents has been widely explored, advances have been slow and the efficacy of these agents has reached a plateau of median overall survival not higher than 12 months. Therefore, researchers focused their attention on better understanding molecular biology of carcinogenesis and deeper knowledge of the cancer cell phenotype, as well on development of rationally designed drugs that would target specific molecular aberrancies in signal transduction pathways. These targets include cell surface receptors, circulating growth and angiogenic factors and other molecules involved in downstream intracellular signaling pathways, including receptor tyrosine kinases. However, therapeutic advances in gastric cancer are not so encouraging when compared to other solid organ malignancies such as breast and colorectal cancer. This article reviews the role of targeted agents in gastric cancer as single-agent therapy or in combination regimens, including their rational and emerging mechanism of action, current and emerging data. We focused our attention mainly on published phase III studies, therefore cornerstone clinical trials with trastuzumab and bevacizumab have been largely discussed. Phase III studies presented in important international meetings are also reviewed as well phase II published studies and promising new therapies investigated in preclinical or phase I studies. Today, in first-line treatment only trastuzumab has shown significantly increased survival in combination with chemotherapy, whereas ramucirumab as single agent resulted effective in progressing patients, but - despite several disappointing results - these are the proof of principle that targeting the proper molecular aberration is the best way for implementing outcome of therapy.
Current Medicinal Chemistry
Title:Targeted Therapy in Advanced Gastric Carcinoma: The Future is Beginning
Volume: 21 Issue: 8
Author(s): G. Schinzari, A. Cassano, A. Orlandi, M. Basso and C. Barone
Affiliation:
Keywords: c-MET, EGFR, gastric cancer, HER-2, mTOR, VEGF.
Abstract: Gastric cancer represents one of the most common cancer worldwide. Unfortunately, the majority of patients present in advanced stage and outcome still remains poor with high mortality rate despite decreasing incidence and new diagnostic and therapeutic strategies. Although utility of classical chemotherapy agents has been widely explored, advances have been slow and the efficacy of these agents has reached a plateau of median overall survival not higher than 12 months. Therefore, researchers focused their attention on better understanding molecular biology of carcinogenesis and deeper knowledge of the cancer cell phenotype, as well on development of rationally designed drugs that would target specific molecular aberrancies in signal transduction pathways. These targets include cell surface receptors, circulating growth and angiogenic factors and other molecules involved in downstream intracellular signaling pathways, including receptor tyrosine kinases. However, therapeutic advances in gastric cancer are not so encouraging when compared to other solid organ malignancies such as breast and colorectal cancer. This article reviews the role of targeted agents in gastric cancer as single-agent therapy or in combination regimens, including their rational and emerging mechanism of action, current and emerging data. We focused our attention mainly on published phase III studies, therefore cornerstone clinical trials with trastuzumab and bevacizumab have been largely discussed. Phase III studies presented in important international meetings are also reviewed as well phase II published studies and promising new therapies investigated in preclinical or phase I studies. Today, in first-line treatment only trastuzumab has shown significantly increased survival in combination with chemotherapy, whereas ramucirumab as single agent resulted effective in progressing patients, but - despite several disappointing results - these are the proof of principle that targeting the proper molecular aberration is the best way for implementing outcome of therapy.
Export Options
About this article
Cite this article as:
Schinzari G., Cassano A., Orlandi A., Basso M. and Barone C., Targeted Therapy in Advanced Gastric Carcinoma: The Future is Beginning, Current Medicinal Chemistry 2014; 21 (8) . https://dx.doi.org/10.2174/0929867321666131129124054
DOI https://dx.doi.org/10.2174/0929867321666131129124054 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Synthesis and Evaluation of Anti-inflammatory and Analgesic Activities of New 1,2,4-triazole Derivatives
Medicinal Chemistry Antihistamine Use in Dermatologic Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Critical Update and Emerging Trends in Imatinib Treatment for Gastrointestinal Stromal Tumor
Reviews on Recent Clinical Trials The Application of Fungal Beta-glucans for the Treatment of Colon Cancer
Anti-Cancer Agents in Medicinal Chemistry Plant-Derived Polyphenols in Human Health: Biological Activity, Metabolites and Putative Molecular Targets
Current Drug Metabolism Preparation and Characterization of Highly Fluorescent TGA-CdTe Quantum Dot-Hyamine 1622 Additive Composite
Micro and Nanosystems Molecular Mechanisms of Inflammation. Anti-Inflammatory Benefits of Virgin Olive Oil and the Phenolic Compound Oleocanthal
Current Pharmaceutical Design Antiangiogenic Gene Therapy in Cancer
Current Genomics Microarray Analysis of Human Epithelial Cell Responses to Bacterial Interaction
Infectious Disorders - Drug Targets Beta-glucans is a Potential Inhibitor of Ovarian Cancer: Based on Molecular and Biological Aspects
Current Pharmaceutical Biotechnology Appraisal of Saxagliptin as Treatment of Type 2 Diabetes
Current Drug Therapy Amino Acid Derived Prodrugs: An Approach to Improve the Bioavailability of Clinically Approved Drugs
Current Topics in Medicinal Chemistry Targeting the Endocannabinoid System for the Treatment of Cancer – A Practical View
Current Topics in Medicinal Chemistry Risk Assessment and Regulation of Molecular Farming - A Comparison between Europe and US
Current Pharmaceutical Design Known Triterpenes and their Derivatives as Scaffolds for the Development of New Therapeutic Agents for Cancer
Current Medicinal Chemistry Gene Expression Significance in Personalized Medicine of Non-small Cell Lung Cancer and Gene Expression Analyzing Platforms
Current Drug Metabolism Monoclonal Antibodies in Cancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Trifluoroibuprofen Inhibits α-Methylacyl Coenzyme A Racemase (AMACR/P504S), Reduces Cancer Cell Proliferation and Inhibits in vivo Tumor Growth in Aggressive Prostate Cancer Models
Anti-Cancer Agents in Medicinal Chemistry Probiotics in Intestinal and Non-Intestinal Infectious Diseases – Clinical Evidence
Current Pharmaceutical Design Targeting Bacterial Metalloenzymes: A New Strategy for the Development of Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry