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

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Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States. Department of Biology, Temple University, Philadelphia, PA, United States. Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States. Department of Biomedical Sciences, Ohio University, Athens, OH, United States. School of Chemical and Bio Technology, SASTRA University, Thanjavur, Tamil Nadu, India. University of Glasgow, Glasgow, United Kingdom. Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL, United States. Department of Pediatrics, State University of New York, Downstate Medical Center, Brooklyn, NY, United States. Department of BioMedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States. Head and Neck Cancer Biology Laboratory, University of Michigan, Ann Arbor, MI, United States. Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Cientificas, Seville, Spain. Centro di Ingegneria Genetica e Biotecnologia Avanzate, Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, Federico II, Via Pansini 5, 80131 Naples, Italy. Stanford University, Division of Oncology, Department of Medicine and Pathology, Stanford, CA, United States. Department of Pathology, Microbiology, and Immunology, University of South Carolina, School of Medicine, Columbia, SC, United States. School of Biotechnology, Jawaharlal Nehru University, New Delhi, India. Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, British Columbia, Canada. Ovarian and Prostate Cancer Research Laboratory, Guildford, Surrey, United Kingdom. Department of Biology, Alderson Broaddus University, Philippi, WV, United States. Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi, Republic of Korea. Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom. Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway. Cancer Biology Research Laboratory, Southern Connecticut State University, New Haven, CT, United States. School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States. Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Department of Oncology, Istituto Di Ricovero e Cura a Carattere Scientifico - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Department of Cellular and Molecular Biology, the University of Texas Health Science Center at Tyler, Tyler, TX, United States. Children's Medical Center Research Institute, University of Texas - Southwestern Medical Center, Dallas, TX, United States. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, United States. Department of Surgery and Cancer Biology, Division of Surgical Oncology, Vanderbilt University School of Medicine, Nashville, TN, United States. Department of Medicine, Duke University Medical Center, Durham, NC, United States. Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, Scotland, United Kingdom. College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, United States. Discipline of Nutrition and Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand. Dipartimento di Scienze per la Qualità della Vita Alma Mater Studiorum-Università di Bologna, Rimini, Italy. 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Seminars in cancer biology. 2015;(Suppl):S276-S304
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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.

Methodological quality

Publication Type : Review

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