Abstract
Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based pharmacology and chemical biology strategies have uncovered a much more complex interaction between drugs and the human proteome than was previously anticipated. In this mini-review we assess the progress and potential of drug polypharmacology in biomarker-driven precision oncology. Polypharmacology not only provides great opportunities for drug repurposing to exploit off-target effects in a new single-target indication but through simultaneous blockade of multiple targets or pathways offers exciting opportunities to slow, overcome or even prevent inherent or adaptive drug resistance. We highlight the many challenges associated with exploiting known or desired polypharmacology in drug design and development, and assess computational and experimental methods to uncover unknown polypharmacology. A comprehensive understanding of the intricate links between polypharmacology, efficacy and safety is urgently needed if we are to tackle the enduring challenge of cancer drug resistance and to fully exploit polypharmacology for the ultimate benefit of cancer patients.
Keywords: Polypharmacology, systems pharmacology, off-target, precision oncology, biomarker, target profiling, side-effects, multi-target drug design.
Current Pharmaceutical Design
Title:Polypharmacology in Precision Oncology: Current Applications and Future Prospects
Volume: 22 Issue: 46
Author(s): Albert A. Antolin, Paul Workman, Jordi Mestres and Bissan Al-Lazikani
Affiliation:
Keywords: Polypharmacology, systems pharmacology, off-target, precision oncology, biomarker, target profiling, side-effects, multi-target drug design.
Abstract: Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based pharmacology and chemical biology strategies have uncovered a much more complex interaction between drugs and the human proteome than was previously anticipated. In this mini-review we assess the progress and potential of drug polypharmacology in biomarker-driven precision oncology. Polypharmacology not only provides great opportunities for drug repurposing to exploit off-target effects in a new single-target indication but through simultaneous blockade of multiple targets or pathways offers exciting opportunities to slow, overcome or even prevent inherent or adaptive drug resistance. We highlight the many challenges associated with exploiting known or desired polypharmacology in drug design and development, and assess computational and experimental methods to uncover unknown polypharmacology. A comprehensive understanding of the intricate links between polypharmacology, efficacy and safety is urgently needed if we are to tackle the enduring challenge of cancer drug resistance and to fully exploit polypharmacology for the ultimate benefit of cancer patients.
Export Options
About this article
Cite this article as:
Antolin A. Albert, Workman Paul, Mestres Jordi and Al-Lazikani Bissan, Polypharmacology in Precision Oncology: Current Applications and Future Prospects, Current Pharmaceutical Design 2016; 22 (46) . https://dx.doi.org/10.2174/1381612822666160923115828
DOI https://dx.doi.org/10.2174/1381612822666160923115828 |
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
-
Glioma: Tryptophan Catabolite and Melatoninergic Pathways Link microRNA, 14-3- 3, Chromosome 4q35, Epigenetic Processes and other Glioma Biochemical Changes
Current Pharmaceutical Design Selective Thyroid Hormone Receptor Modulators
Current Topics in Medicinal Chemistry Targeting the Bone Microenvironment in Metastatic Castration-Resistant Prostate Cancer
Current Drug Targets Osteoprotegerin A Physiological and Pharmacological Inhibitor of Bone Resorption.
Current Pharmaceutical Design L-carnitine: Searching for New Therapeutic Strategy for Sepsis Management
Current Medicinal Chemistry A Comprehensive Review on Phytochemistry and Pharmacological Effects of Stinging Nettle (Urtica dioica)
Current Traditional Medicine Hyperprolactinemia Secondary to Pituitary Microadenoma Versus Haloperidol- A Diagnostic Enigma. A Case Report and Brief Review
Current Drug Safety The Influence of Co-Ligands on Improving Tumor Targeting of <sup>99m</sup>Tc-HYNIC Conjugated Peptides
Mini-Reviews in Medicinal Chemistry Current Advances in Therapy for Metastatic Melanoma
Current Cancer Therapy Reviews The Detrimental Effect of Smoking on Female Fertility and IVF Success
Current Women`s Health Reviews Role of Sequence Variations in <i>AhR</i> Gene Towards Modulating Smoking Induced Lung Cancer Susceptibility in North Indian Population: A Multiple Interaction Analysis
Current Genomics HMGB-1 as a Target for Inflammation Controlling
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Targeting Translation for Treatment of Cancer - A Novel Role for IRES?
Current Cancer Drug Targets Lafora Progressive Myoclonus Epilepsy: Recent Insights into Cell Degeneration
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Targeting MAPK Signalling: Prometheus Fire or Pandoras Box?
Current Pharmaceutical Design Prostate Cancer, miRNAs, Metallothioneins and Resistance to Cytostatic Drugs
Current Medicinal Chemistry Selective Serotonin Re-Uptake Inhibitors for the Treatment of Depression in Coronary Artery Disease and Chronic Heart Failure: Evidence for Pleiotropic Effects
Cardiovascular & Hematological Agents in Medicinal Chemistry Poly(ADP-ribose) Glycohydrolase Deficiency Sensitizes Mouse ES Cells to DNA Damaging Agents
Current Cancer Drug Targets A Mixed Methods Evaluation of the Effects of an Innovative Art-Based Rehabilitation Program for Youths with Stabilized Psychiatric Disorders
Adolescent Psychiatry Cellular Changes, Molecular Pathways and the Immune System Following Photodynamic Treatment
Current Medicinal Chemistry