Abstract
The effectiveness of anticancer therapies relies on the ability of these substances to selectively eliminate the malignant cells with little or no toxicity to normal cells. The isolation in most human tumors of a rare subpopulation of cancer stem cells (CSCs) associated with chemo resistance leads to the “stem cell theory” (SCT). The SCT proposed that eliminating this fraction will eventually cure cancer but experimental data supporting this classical view are controversial and now being gradually replaced by other models. These novel models of cancer biology predict that to cure cancer only drugs or combination of drugs that eliminate all (CSCs and non-CSCs) cancer cells at once (“pankiller drugs”) will be effective. The search for “pankiller drugs” will require tests to assess (i) the elimination of all cancer cells in in vitro systems (ii) the ability to eradicate the tumors and prevent tumor relapse in in vivo systems. However, at present, most drugs are being tested in assays that can only provide a picture of the short term activity of anticancer compounds. This in part explains why only a small fraction of the drugs that enter clinical trials are actually approved for clinical use. This article will provide a concise review of the systems, assays and endpoint parameters routinely used to screen for potential anticancer drugs and propose, based in the current knowledge of cancer biology, a more rationale anticancer drug screening program.
Keywords: System models, assays, endpoint parameter, anticancer, drug screening, preclinical.
Current Medicinal Chemistry
Title:System Models, Assays and Endpoint Parameters to Evaluate Anticancer Compounds During Preclinical Screening
Volume: 21 Issue: 35
Author(s): Juan Sebastian Yakisich
Affiliation:
Keywords: System models, assays, endpoint parameter, anticancer, drug screening, preclinical.
Abstract: The effectiveness of anticancer therapies relies on the ability of these substances to selectively eliminate the malignant cells with little or no toxicity to normal cells. The isolation in most human tumors of a rare subpopulation of cancer stem cells (CSCs) associated with chemo resistance leads to the “stem cell theory” (SCT). The SCT proposed that eliminating this fraction will eventually cure cancer but experimental data supporting this classical view are controversial and now being gradually replaced by other models. These novel models of cancer biology predict that to cure cancer only drugs or combination of drugs that eliminate all (CSCs and non-CSCs) cancer cells at once (“pankiller drugs”) will be effective. The search for “pankiller drugs” will require tests to assess (i) the elimination of all cancer cells in in vitro systems (ii) the ability to eradicate the tumors and prevent tumor relapse in in vivo systems. However, at present, most drugs are being tested in assays that can only provide a picture of the short term activity of anticancer compounds. This in part explains why only a small fraction of the drugs that enter clinical trials are actually approved for clinical use. This article will provide a concise review of the systems, assays and endpoint parameters routinely used to screen for potential anticancer drugs and propose, based in the current knowledge of cancer biology, a more rationale anticancer drug screening program.
Export Options
About this article
Cite this article as:
Yakisich Sebastian Juan, System Models, Assays and Endpoint Parameters to Evaluate Anticancer Compounds During Preclinical Screening, Current Medicinal Chemistry 2014; 21 (35) . https://dx.doi.org/10.2174/09298673113209990009
DOI https://dx.doi.org/10.2174/09298673113209990009 |
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
-
Kernelized Convex Hull based Collaborative Representation for Tumor Classification
Current Proteomics Current State of the Art of New Tubulin Inhibitors in the Clinic
Current Clinical Pharmacology Patent Selections
Recent Patents on Biomarkers Targeted Tumor Immunotherapy: Are Vaccines the Future of Cancer Treatment?
Current Drug Therapy Ribozymes in the Age of Molecular Therapeutics
Current Molecular Medicine Inhibition of HIV-1 Replication by RNA-Based Strategies
Current HIV Research Roles of p75NTR in Maintaining Brain Hemostasis and the Implications for p75NTR-targeted Therapies
Current Alzheimer Research Na, K-ATPase as a Biological Target for Gold(III) Complexes: A Theoretical and Experimental Approach
Current Medicinal Chemistry Protein Kinase C Isozymes as Potential Targets for Anticancer Therapy
Current Cancer Drug Targets Genetically Engineered Stem Cells for Therapeutic Gene Delivery
Current Gene Therapy Nanoparticles in Melanoma
Current Medicinal Chemistry Targeting the Ubiquitin-Proteasome Pathway in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Astrocytes as an HIV Reservoir: Mechanism of HIV Infection
Current HIV Research Functionalized Nanocarriers for Enhanced Bioactive Delivery to Squamous Cell Carcinomas: Targeting Approaches and Related Biopharmaceutical Aspects
Current Pharmaceutical Design Separation and Identification of Antibacterial Chamomile Components Using OPLC, Bioautography and GC-MS
Medicinal Chemistry Nanotechnology and Brain Tumors Drug Delivery
Recent Patents on Nanomedicine Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives
Current Medicinal Chemistry Subject Index to Volume 4
Current Genomics Evolution of the Strategies for Screening and Identifying Human Tumor Antigens
Current Protein & Peptide Science Flavonoids: The Innocuous Agents Offering Protection against Alzheimer’s Disease Through Modulation of Proinflammatory and Apoptotic Pathways
Current Topics in Medicinal Chemistry