Format

Send to

Choose Destination
Semin Cancer Biol. 2015 Dec;35 Suppl:S276-S304. doi: 10.1016/j.semcancer.2015.09.007.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Block KI1, Gyllenhaal C2, Lowe L3, Amedei A4, Amin ARMR5, Amin A6, Aquilano K7, Arbiser J8, Arreola A9, Arzumanyan A10, Ashraf SS11, Azmi AS12, Benencia F13, Bhakta D14, Bilsland A15, Bishayee A16, Blain SW17, Block PB2, Boosani CS18, Carey TE19, Carnero A20, Carotenuto M21, Casey SC22, Chakrabarti M23, Chaturvedi R24, Chen GZ5, Chen H25, Chen S26, Chen YC27, Choi BK28, Ciriolo MR7, Coley HM29, Collins AR30, Connell M25, Crawford S31, Curran CS32, Dabrosin C33, Damia G34, Dasgupta S35, DeBerardinis RJ36, Decker WK37, Dhawan P38, Diehl AME39, Dong JT5, Dou QP12, Drew JE40, Elkord E41, El-Rayes B42, Feitelson MA10, Felsher DW22, Ferguson LR43, Fimognari C44, Firestone GL45, Frezza C46, Fujii H47, Fuster MM48, Generali D49, Georgakilas AG50, Gieseler F51, Gilbertson M52, Green MF53, Grue B54, Guha G14, Halicka D55, Helferich WG56, Heneberg P57, Hentosh P58, Hirschey MD59, Hofseth LJ60, Holcombe RF61, Honoki K47, Hsu HY62, Huang GS63, Jensen LD64, Jiang WG65, Jones LW66, Karpowicz PA67, Keith WN15, Kerkar SP68, Khan GN69, Khatami M70, Ko YH71, Kucuk O5, Kulathinal RJ10, Kumar NB72, Kwon BS73, Le A74, Lea MA75, Lee HY76, Lichtor T77, Lin LT78, Locasale JW79, Lokeshwar BL80, Longo VD81, Lyssiotis CA82, MacKenzie KL83, Malhotra M84, Marino M85, Martinez-Chantar ML86, Matheu A87, Maxwell C25, McDonnell E53, Meeker AK88, Mehrmohamadi M89, Mehta K90, Michelotti GA39, Mohammad RM12, Mohammed SI91, Morre DJ92, Muralidhar V93, Muqbil I12, Murphy MP94, Nagaraju GP42, Nahta R5, Niccolai E95, Nowsheen S96, Panis C97, Pantano F98, Parslow VR43, Pawelec G99, Pedersen PL100, Poore B74, Poudyal D60, Prakash S84, Prince M101, Raffaghello L102, Rathmell JC53, Rathmell WK9, Ray SK23, Reichrath J103, Rezazadeh S104, Ribatti D105, Ricciardiello L106, Robey RB107, Rodier F108, Rupasinghe HPV109, Russo GL110, Ryan EP111, Samadi AK112, Sanchez-Garcia I113, Sanders AJ65, Santini D98, Sarkar M114, Sasada T115, Saxena NK116, Shackelford RE117, Shantha Kumara HMC118, Sharma D119, Shin DM5, Sidransky D120, Siegelin MD121, Signori E122, Singh N123, Sivanand S124, Sliva D125, Smythe C126, Spagnuolo C110, Stafforini DM127, Stagg J128, Subbarayan PR129, Sundin T130, Talib WH131, Thompson SK132, Tran PT133, Ungefroren H51, Vander Heiden MG134, Venkateswaran V135, Vinay DS136, Vlachostergios PJ137, Wang Z138, Wellen KE124, Whelan RL118, Yang ES139, Yang H140, Yang X56, Yaswen P141, Yedjou C142, Yin X48, Zhu J143, Zollo M21.

Author information

1
Block Center for Integrative Cancer Treatment, Skokie, IL, United States. Electronic address: drblock@blockmedical.com.
2
Block Center for Integrative Cancer Treatment, Skokie, IL, United States.
3
Getting to Know Cancer, Truro, Nova Scotia, Canada; Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster, United Kingdom. Electronic address: Leroy.lowe@gettingtoknowcancer.org.
4
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
5
Winship Cancer Institute of Emory University, Atlanta, GA, United States.
6
Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
7
Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
8
Winship Cancer Institute of Emory University, Atlanta, GA, United States; Atlanta Veterans Administration Medical Center, Atlanta, GA, United States; Department of Dermatology, Emory University School of Medicine, Emory University, Atlanta, GA, United States.
9
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States.
10
Department of Biology, Temple University, Philadelphia, PA, United States.
11
Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
12
Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
13
Department of Biomedical Sciences, Ohio University, Athens, OH, United States.
14
School of Chemical and Bio Technology, SASTRA University, Thanjavur, Tamil Nadu, India.
15
University of Glasgow, Glasgow, United Kingdom.
16
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL, United States.
17
Department of Pediatrics, State University of New York, Downstate Medical Center, Brooklyn, NY, United States.
18
Department of BioMedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States.
19
Head and Neck Cancer Biology Laboratory, University of Michigan, Ann Arbor, MI, United States.
20
Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Cientificas, Seville, Spain.
21
Centro di Ingegneria Genetica e Biotecnologia Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, Federico II, Via Pansini 5, 80131 Naples, Italy.
22
Stanford University, Division of Oncology, Department of Medicine and Pathology, Stanford, CA, United States.
23
Department of Pathology, Microbiology, and Immunology, University of South Carolina, School of Medicine, Columbia, SC, United States.
24
School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
25
Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, British Columbia, Canada.
26
Ovarian and Prostate Cancer Research Laboratory, Guildford, Surrey, United Kingdom.
27
Department of Biology, Alderson Broaddus University, Philippi, WV, United States.
28
Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
29
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
30
Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway.
31
Cancer Biology Research Laboratory, Southern Connecticut State University, New Haven, CT, United States.
32
School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.
33
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
34
Department of Oncology, Istituto Di Ricovero e Cura a Carattere Scientifico - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
35
Department of Cellular and Molecular Biology, the University of Texas Health Science Center at Tyler, Tyler, TX, United States.
36
Children's Medical Center Research Institute, University of Texas - Southwestern Medical Center, Dallas, TX, United States.
37
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, United States.
38
Department of Surgery and Cancer Biology, Division of Surgical Oncology, Vanderbilt University School of Medicine, Nashville, TN, United States.
39
Department of Medicine, Duke University Medical Center, Durham, NC, United States.
40
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
41
College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
42
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, United States.
43
Discipline of Nutrition and Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand.
44
Dipartimento di Scienze per la Qualità della Vita Alma Mater Studiorum-Università di Bologna, Rimini, Italy.
45
Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, CA, United States.
46
Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, United Kingdom.
47
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
48
Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, CA, United States.
49
Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Molecular Therapy and Pharmacogenomics Unit, Azienda Ospedaliera Istituti Ospitalieri di Cremona, Cremona, Italy.
50
Physics Department, School of Applied Mathematics and Physical Sciences, National Technical University of Athens, Athens, Greece.
51
First Department of Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
52
Getting to Know Cancer, Guelph, Canada.
53
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States.
54
Departments of Environmental Science, Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
55
Department of Pathology, New York Medical College, Valhalla, NY, United States.
56
University of Illinois at Urbana Champaign, Champaign, IL, United States.
57
Charles University in Prague, Third Faculty of Medicine, Prague, Czech Republic.
58
School of Medical Laboratory and Radiation Sciences, Old Dominion University, Norfolk, VA, United States.
59
Department of Medicine, Duke University Medical Center, Durham, NC, United States; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States.
60
College of Pharmacy, University of South Carolina, Columbia, SC, United States.
61
Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, United States.
62
Department of Life Sciences, Tzu-Chi University, Hualien, Taiwan.
63
Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States.
64
Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
65
Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom.
66
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, United States.
67
University of Windsor, Windsor, Ontario, Canada.
68
Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
69
Henry Ford Hospital, Detroit, MI, United States.
70
Inflammation and Cancer Research, National Cancer Institute (Retired), National Institutes of Health, Bethesda, MD, United States.
71
University of Maryland BioPark, Innovation Center, KoDiscovery, Baltimore, MD, United States.
72
Moffitt Cancer Center, University of South Florida College of Medicine, Tampa, FL, United States.
73
Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi, Republic of Korea; Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, United States.
74
The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
75
New Jersey Medical School, Rutgers University, Newark, NJ, United States.
76
College of Pharmacy, Seoul National University, South Korea.
77
Department of Neurosurgery, Rush University Medical Center, Chicago, IL, United States.
78
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
79
Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
80
Department of Medicine, Georgia Regents University Cancer Center, Augusta, GA, United States.
81
Andrus Gerontology Center, Division of Biogerontology, University of Southern California, Los Angeles, CA, United States.
82
Department of Molecular and Integrative Physiology and Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States.
83
Children's Cancer Institute Australia, Kensington, New South Wales, Australia.
84
Department of Biomedical Engineering, McGill University, Montréal, Canada.
85
Department of Science, University Roma Tre, Rome, Italy.
86
Metabolomic Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Technology Park of Bizkaia, Bizkaia, Spain.
87
Biodonostia Institute, Gipuzkoa, Spain.
88
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
89
Field of Genetics, Genomics, and Development, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States.
90
Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
91
Department of Comparative Pathobiology, Purdue University Center for Cancer Research, West Lafayette, IN, United States.
92
Mor-NuCo, Inc, Purdue Research Park, West Lafayette, IN, United States.
93
Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States.
94
MRC Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Hills Road, Cambridge, United Kingdom.
95
University of Florence, Florence, Italy.
96
Medical Scientist Training Program, Mayo Graduate School, Mayo Medical School, Mayo Clinic, Rochester, MN, United States.
97
Laboratory of Inflammatory Mediators, State University of West Paraná, UNIOESTE, Paraná, Brazil.
98
Medical Oncology Department, University Campus Bio-Medico, Rome, Italy.
99
Center for Medical Research, University of Tübingen, Tübingen, Germany.
100
Departments of Biological Chemistry and Oncology, Member at Large, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.
101
Department of Otolaryngology-Head and Neck, Medical School, University of Michigan, Ann Arbor, MI, United States.
102
Laboratory of Oncology, Istituto Giannina Gaslini, Genoa, Italy.
103
Center for Clinical and Experimental Photodermatology, Clinic for Dermatology, Venerology and Allergology, The Saarland University Hospital, Homburg, Germany.
104
Department of Biology, University of Rochester, Rochester, NY, United States.
105
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy & National Cancer Institute Giovanni Paolo II, Bari, Italy.
106
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
107
White River Junction Veterans Affairs Medical Center, White River Junction, VT, United States; Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
108
Centre de Rechercher du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Montréal, Quebec, Canada; Université de Montréal, Département de Radiologie, Radio-Oncologie et Médicine Nucléaire, Montréal, Quebec, Canada.
109
Department of Environmental Sciences, Faculty of Agriculture and Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
110
Institute of Food Sciences National Research Council, Avellino, Italy.
111
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States.
112
Sanus Biosciences, San Diego, CA, United States.
113
Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Salamanca, Spain.
114
Department of Biology, University of Miami, Miami, FL, United States.
115
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
116
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
117
Department of Pathology, Louisiana State University, Health Shreveport, Shreveport, LA, United States.
118
Department of Surgery, St. Luke's Roosevelt Hospital, New York, NY, United States.
119
Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States.
120
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
121
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United States.
122
National Research Council, Institute of Translational Pharmacology, Rome, Italy.
123
Advanced Molecular Science Research Centre (Centre for Advanced Research), King George's Medical University, Lucknow, Uttar Pradesh, India.
124
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
125
DSTest Laboratories, Purdue Research Park, Indianapolis, IN, United States.
126
Department of Biomedical Science, Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom.
127
Huntsman Cancer Institute and Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States.
128
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Faculté de Pharmacie et Institut du Cancer de Montréal, Montréal, Quebec, Canada.
129
Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States.
130
Department of Molecular Diagnostics, Sentara Healthcare, Norfolk, VA, United States.
131
Department of Clinical Pharmacy and Therapeutics, Applied Science University, Amman, Jordan.
132
Department of Surgery, Royal Adelaide Hospital, Adelaide, Australia.
133
Departments of Radiation Oncology & Molecular Radiation Sciences, Oncology and Urology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
134
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States.
135
Department of Surgery, University of Toronto, Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
136
Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, United States.
137
Department of Internal Medicine, New York University Lutheran Medical Center, Brooklyn, New York, NY, United States.
138
Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
139
Department of Radiation Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, United States.
140
The School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China.
141
Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, CA, United States.
142
Department of Biology, Jackson State University, Jackson, MS, United States.
143
Washington State University College of Pharmacy, Spokane, WA, United States.

Abstract

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.

KEYWORDS:

Cancer hallmarks; Integrative medicine; Multi-targeted; Phytochemicals; Targeted therapy

PMID:
26590477
PMCID:
PMC4819002
DOI:
10.1016/j.semcancer.2015.09.007
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substance, Grant support

Publication types

MeSH terms

Substance

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center