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      Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer

      a , b , * , a , c

      Biochimica et Biophysica Acta. Reviews on Cancer

      Elsevier

      Repurposing in oncology, Colorectal cancer, Drug repositioning, Mechanism of action, Signaling pathways, On/off-target effects, Polypharmacology, Side effects, Omics, Phenotypes, Computational approaches, A-II, angiotensin-II, Ab, antibody, ACF, aberrant crypt foci, ARD, adverse drug reactions, AMPK, adenosine monophosphate-activated protein kinase, AT1R, angiotensin II type 1 receptor, ATC, Anatomical Therapeutic Chemical classification, CaPP3, Cancer Prevention Project 3, CHAT, cancer hallmarks analytics tool, CMap, Connectivity Map, COX-2, cyclooxygenase-2, CRC, colorectal carcinoma, DCF, Diclofenac, EGFR, epidermal growth factor receptor, EMA, European Medicines Agency, FAP, familial adenomatous polyposis, FMCM, Functional Module Connectivity Map, FFN, function-function networks, GSToP, gene-selection-by-trend-of-progression procedure, GWAS, Genome-Wide Association Studies, HERV, human endogenous retrovirus, KEGG, Kyoto Encyclopedia of Genes and Genomes, LBD, literature-based discovery, LINCS, Library of Integrated Network-Based Cellular Signatures, MANTRA, Mode of Action by NeTwoRk Analysis, MRC, Medical Research Council, NSAID, non-steroidal anti-inflammatory drug, NTID, narrow therapeutic index drug, OS, overall survival, PFS, progression free survival, Pl3K, phosphatidylinositol 3-kinase, POG, Personalized OncoGenomic, PREDICT, PREdicting Drug IndiCaTions, RAR α, retinoic acid receptor alpha, ReDo, Repurposing Drugs in Oncology, RRM2, human ribonucleotide reductase 2, SEA, Similarity Ensemble Approach, sLA, sialyl Lewis-A antigen, SMILE, simplified molecular-input line-entry system, SVM, Support Vector Machine, TKI, tyrosine kinase inhibitors, TOP2A, Topisomarase 2-α, USPSTF, U.S. Preventive Services Task Force

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          Abstract

          The strategy of using existing drugs originally developed for one disease to treat other indications has found success across medical fields. Such drug repurposing promises faster access of drugs to patients while reducing costs in the long and difficult process of drug development. However, the number of existing drugs and diseases, together with the heterogeneity of patients and diseases, notably including cancers, can make repurposing time consuming and inefficient. The key question we address is how to efficiently repurpose an existing drug to treat a given indication. As drug efficacy remains the main bottleneck for overall success, we discuss the need for machine-learning computational methods in combination with specific phenotypic studies along with mechanistic studies, chemical genetics and omics assays to successfully predict disease-drug pairs. Such a pipeline could be particularly important to cancer patients who face heterogeneous, recurrent and metastatic disease and need fast and personalized treatments. Here we focus on drug repurposing for colorectal cancer and describe selected therapeutics already repositioned for its prevention and/or treatment as well as potential candidates. We consider this review as a selective compilation of approaches and methodologies, and argue how, taken together, they could bring drug repurposing to the next level.

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          Most cited references 228

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          Hallmarks of Cancer: The Next Generation

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              Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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                Author and article information

                Affiliations
                [a ]School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland
                [b ]Translational Research Center in Oncohaematology, University of Geneva, Rue Michel Servet 1, 1211 Geneva 4, Switzerland
                [c ]Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Rue Michel Servet 1, 1211 Geneva 4, Switzerland
                Author notes
                [* ]Corresponding author at: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland. Patrycja.Nowak-Sliwinska@ 123456unige.ch
                Contributors
                Journal
                Biochim Biophys Acta Rev Cancer
                Biochim Biophys Acta Rev Cancer
                Biochimica et Biophysica Acta. Reviews on Cancer
                Elsevier
                0304-419X
                1879-2561
                1 April 2019
                April 2019
                : 1871
                : 2
                : 434-454
                S0304-419X(19)30037-X
                10.1016/j.bbcan.2019.04.005
                6528778
                31034926
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                Categories
                Article

                uspstf, u.s. preventive services task force, repurposing in oncology, colorectal cancer, drug repositioning, mechanism of action, signaling pathways, on/off-target effects, polypharmacology, side effects, omics, phenotypes, computational approaches, a-ii, angiotensin-ii, ab, antibody, acf, aberrant crypt foci, ard, adverse drug reactions, ampk, adenosine monophosphate-activated protein kinase, at1r, angiotensin ii type 1 receptor, atc, anatomical therapeutic chemical classification, capp3, cancer prevention project 3, chat, cancer hallmarks analytics tool, cmap, connectivity map, cox-2, cyclooxygenase-2, crc, colorectal carcinoma, dcf, diclofenac, egfr, epidermal growth factor receptor, ema, european medicines agency, fap, familial adenomatous polyposis, fmcm, functional module connectivity map, ffn, function-function networks, gstop, gene-selection-by-trend-of-progression procedure, gwas, genome-wide association studies, herv, human endogenous retrovirus, kegg, kyoto encyclopedia of genes and genomes, lbd, literature-based discovery, lincs, library of integrated network-based cellular signatures, mantra, mode of action by network analysis, mrc, medical research council, nsaid, non-steroidal anti-inflammatory drug, ntid, narrow therapeutic index drug, os, overall survival, pfs, progression free survival, pl3k, phosphatidylinositol 3-kinase, pog, personalized oncogenomic, predict, predicting drug indications, rar α, retinoic acid receptor alpha, redo, repurposing drugs in oncology, rrm2, human ribonucleotide reductase 2, sea, similarity ensemble approach, sla, sialyl lewis-a antigen, smile, simplified molecular-input line-entry system, svm, support vector machine, tki, tyrosine kinase inhibitors, top2a, topisomarase 2-α

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