Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

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

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      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.

      Related collections

      Most cited references 228

      • Record: found
      • Abstract: found
      • Article: found

      Hallmarks of Cancer: The Next Generation

      The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Inflammation and cancer.

        Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          The blockade of immune checkpoints in cancer immunotherapy.

          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.
            Bookmark

            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
            31034926
            6528778
            S0304-419X(19)30037-X
            10.1016/j.bbcan.2019.04.005
            © 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

            Comments

            Comment on this article