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

Keith I. Block, Charlotte Gyllenhaal, Leroy Lowe, Amedeo Amedei, A. R.M. Ruhul Amin, Amr Amin, Katia Aquilano, Jack Arbiser, Alexandra Arreola, Alla Arzumanyan, S. Salman Ashraf, Asfar S. Azmi, Fabian Benencia, Dipita Bhakta, Alan Bilsland, Anupam Bishayee, Stacy W. Blain, Penny B. Block, Chandra S. Boosani, Thomas E. CareyAmancio Carnero, Marianeve Carotenuto, Stephanie C. Casey, Mrinmay Chakrabarti, Rupesh Chaturvedi, Georgia Zhuo Chen, Helen Chen, Sophie Chen, Yi Charlie Chen, Beom K. Choi, Maria Rosa Ciriolo, Helen M. Coley, Andrew R. Collins, Marisa Connell, Sarah Crawford, Colleen S. Curran, Charlotta Dabrosin, Giovanna Damia, Santanu Dasgupta, Ralph J. DeBerardinis, William K. Decker, Punita Dhawan, Anna Mae E. Diehl, Jin Tang Dong, Q. Ping Dou, Janice E. Drewa, Eyad Elkord, Bassel El-Rayes, Mark A. Feitelson, Dean W. Felsher, Lynnette R. Ferguson, Carmela Fimognari, Gary L. Firestone, Christian Frezza, Hiromasa Fujii, Mark M. Fuster, Daniele Generali, Alexandros G. Georgakilas, Frank Gieseler, Michael Gilbertson, Michelle F. Green, Brendan Grue, Gunjan Guhal, Dorota Halicka, William G. Helferich, Petr Heneberg, Patricia Hentosh, Matthew D. Hirschey, Lorne J. Hofseth, Randall F. Holcombe, Kanya Honoki, Hsue Yin Hsu, Gloria S. Huang, Lasse D. Jensen, Wen G. Jiang, Lee W. Jones, Phillip A. Karpowicz, W. Nicol Keith, Sid P. Kerkar, Gazala N. Khan, Mahin Khatami, Young H. Ko, Omer Kucuk, Rob J. Kulathinal, Nagi B. Kumar, Byoung S. Kwon, Anne Le, Michael A. Leab, Ho Young Lee, Terry Lichtor, Liang Tzung Lin, Jason W. Locasale, Bal L. Lokeshwar, Valter D. Longo, Costas A. Lyssiotis, Karen L. MacKenzie, Meenakshi Malhotra, Maria Marino, Maria L. Martinez-Chantar, Ander Matheu, Christopher Maxwell, Eoin McDonnell, Alan K. Meeker, Mahya Mehrmohamadi, Kapil Mehta, Gregory A. Michelotti, Ramzi M. Mohammad, Sulma I. Mohammed, D. James Morre, Vinayak Muralidhar, Irfana Muqbil, Michael P. Murphy, Ganji Purnachandra Nagaraju, Rita Nahta, Elena Niccolai, Somaira Nowsheen, Carolina Panis, Francesco Pantano, Virginia R. Parslow, Graham Pawelec, Peter L. Pedersen, Brad Poore, Deepak Poudyal, Satya Prakash, Mark Prince, Lizzia Raffaghello, Jeffrey C. Rathmell, W. Kimryn Rathmell, Swapan K. Ray, Jörg Reichrath, Sarallah Rezazadeh, Domenico Ribatti, Luigi Ricciardiello, R. Brooks Robey, Francis Rodier, H. P.Vasantha Rupasinghe, Gian Luigi Russo, Elizabeth P. Ryan, Abbas K. Samadi, Isidro Sanchez-Garcia, Andrew J. Sanders, Daniele Santini, Malancha Sarkar, Tetsuro Sasada, Neeraj K. Saxena, Rodney E. Shackelford, H. M.C. Shantha Kumara, Dipali Sharma, Dong M. Shin, David Sidransky, Markus David Siegelin, Emanuela Signori, Neetu Singh, Sharanya Sivanand, Daniel Sliva, Carl Smythe, Carmela Spagnuolo, Diana M. Stafforini, John Stagg, Pochi R. Subbarayan, Tabetha Sundin, Wamidh H. Talib, Sarah K. Thompson, Phuoc T. Tran, Hendrik Ungefroren, Matthew G. Vander Heiden, Vasundara Venkateswaran, Dass S. Vinay, Panagiotis J. Vlachostergios, Zongwei Wang, Kathryn E. Wellen, Richard L. Whelan, Eddy S. Yang, Huanjie Yang, Xujuan Yang, Paul Yaswen, Clement Yedjou, Xin Yin, Jiyue Zhu, Massimo Zollo

Research output: Contribution to journalReview article

156 Citations (Scopus)

Abstract

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational 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 aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships 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. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered.

Original languageEnglish
Pages (from-to)S276-S304
Number of pages29
JournalSEMINARS IN CANCER BIOLOGY
Volume35
Issue numberSupp.
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

Bibliographical note

'This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).'

Keywords

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

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  • Cite this

    Block, K. I., Gyllenhaal, C., Lowe, L., Amedei, A., Ruhul Amin, A. R. M., Amin, A., Aquilano, K., Arbiser, J., Arreola, A., Arzumanyan, A., Salman Ashraf, S., Azmi, A. S., Benencia, F., Bhakta, D., Bilsland, A., Bishayee, A., Blain, S. W., Block, P. B., Boosani, C. S., ... Zollo, M. (2015). Designing a broad-spectrum integrative approach for cancer prevention and treatment. SEMINARS IN CANCER BIOLOGY, 35(Supp.), S276-S304. https://doi.org/10.1016/j.semcancer.2015.09.007