Abstract
Cancer remains a fundamental burden to public health despite substantial efforts aimed at developing effective chemotherapeutics and significant advances in chemotherapeutic regimens. The major challenge in anti-cancer drug design is to selectively target cancer cells with high specificity. Research into treating malignancies by targeting altered metabolism in cancer cells is supported by computational approaches, which can take a leading role in identifying candidate targets for anti-cancer therapy as well as assist in the discovery and optimisation of anti-cancer agents. Natural products appear to have privileged structures for anti-cancer drug development and the bulk of this particularly valuable chemical space still remains to be explored. In this review we aim to provide a comprehensive overview of current strategies for computer-guided anti-cancer drug development. We start with a discussion of state-of-the art bioinformatics methods applied to the identification of novel anti-cancer targets, including machine learning techniques, the Connectivity Map and biological network analysis. This is followed by an extensive survey of molecular modelling and cheminformatics techniques employed to develop agents targeting proteins involved in the glycolytic, lipid, NAD+, mitochondrial (TCA cycle), amino acid and nucleic acid metabolism of cancer cells. A dedicated section highlights the most promising strategies to develop anti-cancer therapeutics from natural products and the role of metabolism and some of the many targets which are under investigation are reviewed. Recent success stories are reported for all the areas covered in this review. We conclude with a brief summary of the most interesting strategies identified and with an outlook on future directions in anti-cancer drug development.
Keywords: Cancer, anti-cancer drugs, chemotherapy, metabolism, computational model, bioinformatics, cheminformatics, molecular modelling, natural products, anti-metabolites
Current Pharmaceutical Design
Title:Anti-cancer Drug Development: Computational Strategies to Identify and Target Proteins Involved in Cancer Metabolism
Volume: 19 Issue: 4
Author(s): Lora Mak, Sonia Liggi, Lu Tan, Kanthida Kusonmano, Judith M. Rollinger, Alexios Koutsoukas, Robert C. Glen, Johannes Kirchmair
Affiliation:
Keywords: Cancer, anti-cancer drugs, chemotherapy, metabolism, computational model, bioinformatics, cheminformatics, molecular modelling, natural products, anti-metabolites
Abstract: Cancer remains a fundamental burden to public health despite substantial efforts aimed at developing effective chemotherapeutics and significant advances in chemotherapeutic regimens. The major challenge in anti-cancer drug design is to selectively target cancer cells with high specificity. Research into treating malignancies by targeting altered metabolism in cancer cells is supported by computational approaches, which can take a leading role in identifying candidate targets for anti-cancer therapy as well as assist in the discovery and optimisation of anti-cancer agents. Natural products appear to have privileged structures for anti-cancer drug development and the bulk of this particularly valuable chemical space still remains to be explored. In this review we aim to provide a comprehensive overview of current strategies for computer-guided anti-cancer drug development. We start with a discussion of state-of-the art bioinformatics methods applied to the identification of novel anti-cancer targets, including machine learning techniques, the Connectivity Map and biological network analysis. This is followed by an extensive survey of molecular modelling and cheminformatics techniques employed to develop agents targeting proteins involved in the glycolytic, lipid, NAD+, mitochondrial (TCA cycle), amino acid and nucleic acid metabolism of cancer cells. A dedicated section highlights the most promising strategies to develop anti-cancer therapeutics from natural products and the role of metabolism and some of the many targets which are under investigation are reviewed. Recent success stories are reported for all the areas covered in this review. We conclude with a brief summary of the most interesting strategies identified and with an outlook on future directions in anti-cancer drug development.
Export Options
About this article
Cite this article as:
Lora Mak, Sonia Liggi, Lu Tan, Kanthida Kusonmano, Judith M. Rollinger, Alexios Koutsoukas, Robert C. Glen, Johannes Kirchmair , Anti-cancer Drug Development: Computational Strategies to Identify and Target Proteins Involved in Cancer Metabolism, Current Pharmaceutical Design 2013; 19 (4) . https://dx.doi.org/10.2174/1381612811306040532
DOI https://dx.doi.org/10.2174/1381612811306040532 |
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
-
A Computational Approach to Identify Novel Potential Precursor miRNAs and their Targets from Hepatocellular Carcinoma Cells
Current Bioinformatics Meet Our Editorial Board Member
Anti-Cancer Agents in Medicinal Chemistry Tissue Distribution of Glutamate Carboxypeptidase II (GCPII) with a Focus on the Central and Peripheral Nervous System
Current Medicinal Chemistry Predicting Drug Metabolism Induction In Silico
Current Topics in Medicinal Chemistry Aurora B Kinase and Passenger Proteins as Targets for Cancer Therapy
Current Enzyme Inhibition Nanomedicines as Cancer Therapeutics: Current Status
Current Cancer Drug Targets Meet Our Editor
Anti-Cancer Agents in Medicinal Chemistry Chemical Biology of mGlu4 Receptor Activation: Dogmas, Challenges, Strategies and Opportunities
Current Topics in Medicinal Chemistry Pharmacogenomics of Osteoporosis
Current Pharmacogenomics Biological Properties of Citrus Flavonoids Pertaining to Cancer and Inflammation
Current Medicinal Chemistry Role of Oxygen in Cancer: Looking Beyond Hypoxia
Anti-Cancer Agents in Medicinal Chemistry Meet Our Regional Editor
Anti-Cancer Agents in Medicinal Chemistry Radiation-Induced Pulmonary Epithelial-Mesenchymal Transition: A Review on Targeting Molecular Pathways and Mediators
Current Drug Targets Biospecific Interaction Analysis (BIA) as a Tool for the Design and Development of Gene Transcription Modifiers
Current Medicinal Chemistry - Anti-Cancer Agents Development and Application of Peptide-Based Radiopharmaceuticals
Anti-Cancer Agents in Medicinal Chemistry Anticancer Activity of Ferrocenylthiosemicarbazones
Anti-Cancer Agents in Medicinal Chemistry Application of Metabolomics in Drug Discovery, Development and Theranostics
Current Metabolomics Systemic Treatment of Chest Tumors: Highlighting Some Differences Between Eastern and Western Countries
Current Cancer Therapy Reviews Synthesis, Cytotoxic Evaluation, and Molecular Docking Studies of N-(7- hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide/benzamide Analogues
Letters in Drug Design & Discovery Antioxidants in Wild Mushrooms
Current Medicinal Chemistry