title: A multi-targeted approach to suppress tumor-promoting inflammation.
abstract: Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.
authors.affiliation: Sanus Biosciences, San Diego, CA, United States.
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authors.initials: AK
authors.lastname: Samadi
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Alan
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authors.lastname: Bilsland
authors.affiliation: Physics Department, School of Applied Mathematics and Physical Sciences, National Technical University of Athens, Athens, Greece.
authors.forename: Alexandros G
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authors.lastname: Georgakilas
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Amedeo
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authors.lastname: Amedei
authors.affiliation: Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates; Faculty of Science, Cairo University, Cairo, Egypt.
authors.forename: Amr
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authors.lastname: Amin
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL, United States.
authors.forename: Anupam
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authors.affiliation: Department of Pathology, Wayne State Univeristy, Karmanos Cancer Center, Detroit, MI, USA.
authors.forename: Asfar S
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authors.affiliation: Department of Urology, University of Miami, Miller School of Medicine, Miami, FL, United States; Miami Veterans Administration Medical Center, Miami, FL, United States.
authors.forename: Bal L
authors.initials: BL
authors.lastname: Lokeshwar
authors.affiliation: Department of Environmental Science, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Brendan
authors.initials: B
authors.lastname: Grue
authors.affiliation: Laboratory of Inflammatory Mediators, State University of West Paraná, UNIOESTE, Paraná, Brazil.
authors.forename: Carolina
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authors.affiliation: Department of BioMedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Boosani
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, United States.
authors.forename: Deepak
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authors.lastname: Poudyal
authors.affiliation: Huntsman Cancer Institute and Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Stafforini
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India.
authors.forename: Dipita
authors.initials: D
authors.lastname: Bhakta
authors.affiliation: University of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Niccolai
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India.
authors.forename: Gunjan
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authors.lastname: Guha
authors.affiliation: Department of Environmental Sciences, Faculty of Agriculture and Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: H P
authors.initials: HP
authors.lastname: Vasantha Rupasinghe
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Hiromasa
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authors.lastname: Fujii
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Kanya
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authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Kapil
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authors.lastname: Mehta
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Katia
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authors.affiliation: Getting to Know Cancer, Truro, Nova Scotia, Canada. Electronic address: leroy.lowe@gettingtoknowcancer.org.
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authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, United States.
authors.forename: Lorne J
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authors.lastname: Hofseth
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Luigi
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authors.lastname: Ricciardiello
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Ciriolo
authors.affiliation: Advanced Molecular Science Research Centre (Centre for Advanced Research), King George's Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Neetu
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authors.affiliation: Department of Surgery, St. Luke's Roosevelt Hospital, New York, NY, United States.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Whelan
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Rupesh
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authors.lastname: Chaturvedi
authors.affiliation: Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: S Salman
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authors.affiliation: Department of Surgery, St. Luke's Roosevelt Hospital, New York, NY, United States.
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authors.initials: HMC
authors.lastname: Shantha Kumara
authors.affiliation: Medical Scientist Training Program, Mayo Graduate School, Mayo Medical School, Mayo Clinic, Rochester, MN, United States.
authors.forename: Somaira
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authors.lastname: Nowsheen
authors.affiliation: Department of Comparative Pathobiology, Purdue University Center for Cancer Research, West Lafayette, IN, United States.
authors.forename: Sulma I
authors.initials: SI
authors.lastname: Mohammed
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: W Nicol
authors.initials: WN
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authors.affiliation: University of Illinois at Urbana Champaign, Champaign, IL, United States.
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
authors.affiliation: University of Illinois at Urbana Champaign, Champaign, IL, United States.
authors.forename: Xujuan
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authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D018740:Genetic Heterogeneity / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins
keywords: Cancer; Hallmarks; Inflammation; Phytochemicals; Tumor