title: Cancer prevention and therapy through the modulation of the tumor microenvironment.
abstract: Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer.
authors: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA, United States.
authors: Stephanie C
authors: SC
authors: Casey
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Amedeo
authors: A
authors: Amedei
authors: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors: Katia
authors: K
authors: Aquilano
authors: Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States.
authors: Asfar S
authors: AS
authors: Azmi
authors: Department of Biomedical Sciences, Ohio University, Athens, OH, United States.
authors: Fabian
authors: F
authors: Benencia
authors: School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, Tamil Nadu, India.
authors: Dipita
authors: D
authors: Bhakta
authors: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Alan E
authors: AE
authors: Bilsland
authors: Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States.
authors: Chandra S
authors: CS
authors: Boosani
authors: Ovarian and Prostate Cancer Research Laboratory, Guildford, Surrey, United Kingdom.
authors: Sophie
authors: S
authors: Chen
authors: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors: Maria Rosa
authors: MR
authors: Ciriolo
authors: Department of Biology, Southern Connecticut State University, New Haven, CT, United States.
authors: Sarah
authors: S
authors: Crawford
authors: Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan.
authors: Hiromasa
authors: H
authors: Fujii
authors: Physics Department, School of Applied Mathematics and Physical Sciences, National Technical University of Athens, Athens, Greece.
authors: Alexandros G
authors: AG
authors: Georgakilas
authors: School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, Tamil Nadu, India.
authors: Gunjan
authors: G
authors: Guha
authors: New York Medical College, Valhalla, NY, United States.
authors: Dorota
authors: D
authors: Halicka
authors: University of Illinois at Urbana-Champaign, Champaign-Urbana, IL, United States.
authors: William G
authors: WG
authors: Helferich
authors: Charles University in Prague, Third Faculty of Medicine, Prague, Czech Republic.
authors: Petr
authors: P
authors: Heneberg
authors: Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan.
authors: Kanya
authors: K
authors: Honoki
authors: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: W Nicol
authors: WN
authors: Keith
authors: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
authors: Sid P
authors: SP
authors: Kerkar
authors: Department of Comparative Pathobiology, Purdue University Center for Cancer Research, West Lafayette, IN, United States.
authors: Sulma I
authors: SI
authors: Mohammed
authors: University of Florence, Florence, Italy.
authors: Elena
authors: E
authors: Niccolai
authors: Medical Scientist Training Program, Mayo Graduate School, Mayo Medical School, Mayo Clinic, Rochester, MN, United States.
authors: Somaira
authors: S
authors: Nowsheen
authors: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Nova Scotia, Canada.
authors: H P
authors: HP
authors: Vasantha Rupasinghe
authors: Sanus Biosciences, San Diego, United States.
authors: Abbas
authors: A
authors: Samadi
authors: Advanced Molecular Science Research Centre (Centre for Advanced Research), King George's Medical University, Lucknow, Uttar Pradesh, India.
authors: Neetu
authors: N
authors: Singh
authors: Department of Clinical Pharmacy and Therapeutics, Applied Science University, Amman, Jordan.
authors: Wamidh H
authors: WH
authors: Talib
authors: Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors: Vasundara
authors: V
authors: Venkateswaran
authors: Mount Sinai Roosevelt Hospital, Icahn Mount Sinai School of Medicine, New York City, NY, United States.
authors: Richard L
authors: RL
authors: Whelan
authors: University of Illinois at Urbana-Champaign, Champaign-Urbana, IL, United States.
authors: Xujuan
authors: X
authors: Yang
authors: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: dfelsher@stanford.edu.
authors: Dean W
authors: DW
authors: Felsher
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer biology; Cancer prevention; Cancer therapy; Tumor microenvironment