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 Carey & 160 others Amancio 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 Drew, 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 Guha, 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 Lea, 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 journalArticle

115 Citations (Scopus)
6 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)S276-S304
Number of pages19
JournalSeminars in cancer biology
Volume35
Issue numberSupplement
Early online date18 Nov 2015
DOIs
Publication statusPublished - Dec 2015

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Neoplasms
Tumor Microenvironment
Recurrence
Therapeutics
Genetic Heterogeneity
Poisons
Phytochemicals
Advisory Committees
Phenotype
Safety
Costs and Cost Analysis

Keywords

  • multi-targeted
  • cancer hallmarks
  • phytochemicals
  • targeted therapy
  • integrative medicine

Cite this

Block, K. I., Gyllenhaal, C., Lowe, L., Amedei, A., Amin, A. R. M. R., Amin, A., ... Zollo, M. (2015). Designing a broad-spectrum integrative approach for cancer prevention and treatment. Seminars in cancer biology, 35(Supplement), S276-S304. https://doi.org/10.1016/j.semcancer.2015.09.007

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

In: Seminars in cancer biology, Vol. 35, No. Supplement, 12.2015, p. S276-S304.

Research output: Contribution to journalArticle

Block, KI, Gyllenhaal, C, Lowe, L, Amedei, A, Amin, ARMR, Amin, A, Aquilano, K, Arbiser, J, Arreola, A, Arzumanyan, A, Ashraf, SS, Azmi, AS, Benencia, F, Bhakta, D, Bilsland, A, Bishayee, A, Blain, SW, Block, PB, Boosani, CS, Carey, TE, Carnero, A, Carotenuto, M, Casey, SC, Chakrabarti, M, Chaturvedi, R, Chen, GZ, Chen, H, Chen, S, Chen, YC, Choi, BK, Ciriolo, MR, Coley, HM, Collins, AR, Connell, M, Crawford, S, Curran, CS, Dabrosin, C, Damia, G, Dasgupta, S, DeBerardinis, RJ, Decker, WK, Dhawan, P, Diehl, AME, Dong, J-T, Dou, QP, Drew, JE, Elkord, E, El-Rayes, B, Feitelson, MA, Felsher, DW, Ferguson, LR, Fimognari, C, Firestone, GL, Frezza, C, Fujii, H, Fuster, MM, Generali, D, Georgakilas, AG, Gieseler, F, Gilbertson, M, Green, MF, Grue, B, Guha, G, Halicka, D, Helferich, WG, Heneberg, P, Hentosh, P, Hirschey, MD, Hofseth, LJ, Holcombe, RF, Honoki, K, Hsu, H-Y, Huang, GS, Jensen, LD, Jiang, WG, Jones, LW, Karpowicz, PA, Keith, WN, Kerkar, SP, Khan, GN, Khatami, M, Ko, YH, Kucuk, O, Kulathinal, RJ, Kumar, NB, Kwon, BS, Le, A, Lea, MA, Lee, H-Y, Lichtor, T, Lin, L-T, Locasale, JW, Lokeshwar, BL, Longo, VD, Lyssiotis, CA, MacKenzie, KL, Malhotra, M, Marino, M, Martinez-Chantar, ML, Matheu, A, Maxwell, C, McDonnell, E, Meeker, AK, Mehrmohamadi, M, Mehta, K, Michelotti, GA, Mohammad, RM, Mohammed, SI, Morre, DJ, Muralidhar, V, Muqbil, I, Murphy, MP, Nagaraju, GP, Nahta, R, Niccolai, E, Nowsheen, S, Panis, C, Pantano, F, Parslow, VR, Pawelec, G, Pedersen, PL, Poore, B, Poudyal, D, Prakash, S, Prince, M, Raffaghello, L, Rathmell, JC, Rathmell, WK, Ray, SK, Reichrath, J, Rezazadeh, S, Ribatti, D, Ricciardiello, L, Robey, RB, Rodier, F, Rupasinghe, HPV, Russo, GL, Ryan, EP, Samadi, AK, Sanchez-Garcia, I, Sanders, AJ, Santini, D, Sarkar, M, Sasada, T, Saxena, NK, Shackelford, RE, Shantha Kumara, HMC, Sharma, D, Shin, DM, Sidransky, D, Siegelin, MD, Signori, E, Singh, N, Sivanand, S, Sliva, D, Smythe, C, Spagnuolo, C, Stafforini, DM, Stagg, J, Subbarayan, PR, Sundin, T, Talib, WH, Thompson, SK, Tran, PT, Ungefroren, H, Vander Heiden, MG, Venkateswaran, V, Vinay, DS, Vlachostergios, PJ, Wang, Z, Wellen, KE, Whelan, RL, Yang, ES, Yang, H, Yang, X, Yaswen, P, Yedjou, C, Yin, X, Zhu, J & Zollo, M 2015, 'Designing a broad-spectrum integrative approach for cancer prevention and treatment', Seminars in cancer biology, vol. 35, no. Supplement, pp. S276-S304. https://doi.org/10.1016/j.semcancer.2015.09.007
Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin ARMR, Amin A et al. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Seminars in cancer biology. 2015 Dec;35(Supplement):S276-S304. https://doi.org/10.1016/j.semcancer.2015.09.007
Block, Keith I ; Gyllenhaal, Charlotte ; Lowe, Leroy ; Amedei, Amedeo ; Amin, A R M Ruhul ; Amin, Amr ; Aquilano, Katia ; Arbiser, Jack ; Arreola, Alexandra ; Arzumanyan, Alla ; Ashraf, S Salman ; Azmi, Asfar S ; Benencia, Fabian ; Bhakta, Dipita ; Bilsland, Alan ; Bishayee, Anupam ; Blain, Stacy W ; Block, Penny B ; Boosani, Chandra S ; Carey, Thomas E ; Carnero, Amancio ; Carotenuto, Marianeve ; Casey, Stephanie C ; Chakrabarti, Mrinmay ; Chaturvedi, Rupesh ; Chen, Georgia Zhuo ; Chen, Helen ; Chen, Sophie ; Chen, Yi Charlie ; Choi, Beom K ; Ciriolo, Maria Rosa ; Coley, Helen M ; Collins, Andrew R ; Connell, Marisa ; Crawford, Sarah ; Curran, Colleen S ; Dabrosin, Charlotta ; Damia, Giovanna ; Dasgupta, Santanu ; DeBerardinis, Ralph J ; Decker, William K ; Dhawan, Punita ; Diehl, Anna Mae E ; Dong, Jin-Tang ; Dou, Q Ping ; Drew, Janice E ; Elkord, Eyad ; El-Rayes, Bassel ; Feitelson, Mark A ; Felsher, Dean W ; Ferguson, Lynnette R ; Fimognari, Carmela ; Firestone, Gary L ; Frezza, Christian ; Fujii, Hiromasa ; Fuster, Mark M ; Generali, Daniele ; Georgakilas, Alexandros G ; Gieseler, Frank ; Gilbertson, Michael ; Green, Michelle F ; Grue, Brendan ; Guha, Gunjan ; Halicka, Dorota ; Helferich, William G ; Heneberg, Petr ; Hentosh, Patricia ; Hirschey, Matthew D ; Hofseth, Lorne J ; Holcombe, Randall F ; Honoki, Kanya ; Hsu, Hsue-Yin ; Huang, Gloria S ; Jensen, Lasse D ; Jiang, Wen G ; Jones, Lee W ; Karpowicz, Phillip A ; Keith, W Nicol ; Kerkar, Sid P ; Khan, Gazala N ; Khatami, Mahin ; Ko, Young H ; Kucuk, Omer ; Kulathinal, Rob J ; Kumar, Nagi B ; Kwon, Byoung S ; Le, Anne ; Lea, Michael A ; Lee, Ho-Young ; Lichtor, Terry ; Lin, Liang-Tzung ; Locasale, Jason W ; Lokeshwar, Bal L ; Longo, Valter D ; Lyssiotis, Costas A ; MacKenzie, Karen L ; Malhotra, Meenakshi ; Marino, Maria ; Martinez-Chantar, Maria L ; Matheu, Ander ; Maxwell, Christopher ; McDonnell, Eoin ; Meeker, Alan K ; Mehrmohamadi, Mahya ; Mehta, Kapil ; Michelotti, Gregory A ; Mohammad, Ramzi M ; Mohammed, Sulma I ; Morre, D James ; Muralidhar, Vinayak ; Muqbil, Irfana ; Murphy, Michael P ; Nagaraju, Ganji Purnachandra ; Nahta, Rita ; Niccolai, Elena ; Nowsheen, Somaira ; Panis, Carolina ; Pantano, Francesco ; Parslow, Virginia R ; Pawelec, Graham ; Pedersen, Peter L ; Poore, Brad ; Poudyal, Deepak ; Prakash, Satya ; Prince, Mark ; Raffaghello, Lizzia ; Rathmell, Jeffrey C ; Rathmell, W Kimryn ; Ray, Swapan K ; Reichrath, Jörg ; Rezazadeh, Sarallah ; Ribatti, Domenico ; Ricciardiello, Luigi ; Robey, R Brooks ; Rodier, Francis ; Rupasinghe, H P Vasantha ; Russo, Gian Luigi ; Ryan, Elizabeth P ; Samadi, Abbas K ; Sanchez-Garcia, Isidro ; Sanders, Andrew J ; Santini, Daniele ; Sarkar, Malancha ; Sasada, Tetsuro ; Saxena, Neeraj K ; Shackelford, Rodney E ; Shantha Kumara, H M C ; Sharma, Dipali ; Shin, Dong M ; Sidransky, David ; Siegelin, Markus David ; Signori, Emanuela ; Singh, Neetu ; Sivanand, Sharanya ; Sliva, Daniel ; Smythe, Carl ; Spagnuolo, Carmela ; Stafforini, Diana M ; Stagg, John ; Subbarayan, Pochi R ; Sundin, Tabetha ; Talib, Wamidh H ; Thompson, Sarah K ; Tran, Phuoc T ; Ungefroren, Hendrik ; Vander Heiden, Matthew G ; Venkateswaran, Vasundara ; Vinay, Dass S ; Vlachostergios, Panagiotis J ; Wang, Zongwei ; Wellen, Kathryn E ; Whelan, Richard L ; Yang, Eddy S ; Yang, Huanjie ; Yang, Xujuan ; Yaswen, Paul ; Yedjou, Clement ; Yin, Xin ; Zhu, Jiyue ; Zollo, Massimo. / Designing a broad-spectrum integrative approach for cancer prevention and treatment. In: Seminars in cancer biology. 2015 ; Vol. 35, No. Supplement. pp. S276-S304.
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title = "Designing a broad-spectrum integrative approach for cancer prevention and treatment",
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 = "multi-targeted, cancer hallmarks, phytochemicals, targeted therapy, integrative medicine",
author = "Block, {Keith I} and Charlotte Gyllenhaal and Leroy Lowe and Amedeo Amedei and Amin, {A R M Ruhul} and Amr Amin and Katia Aquilano and Jack Arbiser and Alexandra Arreola and Alla Arzumanyan and Ashraf, {S Salman} and Azmi, {Asfar S} and Fabian Benencia and Dipita Bhakta and Alan Bilsland and Anupam Bishayee and Blain, {Stacy W} and Block, {Penny B} and Boosani, {Chandra S} and Carey, {Thomas E} and Amancio Carnero and Marianeve Carotenuto and Casey, {Stephanie C} and Mrinmay Chakrabarti and Rupesh Chaturvedi and Chen, {Georgia Zhuo} and Helen Chen and Sophie Chen and Chen, {Yi Charlie} and Choi, {Beom K} and Ciriolo, {Maria Rosa} and Coley, {Helen M} and Collins, {Andrew R} and Marisa Connell and Sarah Crawford and Curran, {Colleen S} and Charlotta Dabrosin and Giovanna Damia and Santanu Dasgupta and DeBerardinis, {Ralph J} and Decker, {William K} and Punita Dhawan and Diehl, {Anna Mae E} and Jin-Tang Dong and Dou, {Q Ping} and Drew, {Janice E} and Eyad Elkord and Bassel El-Rayes and Feitelson, {Mark A} and Felsher, {Dean W} and Ferguson, {Lynnette R} and Carmela Fimognari and Firestone, {Gary L} and Christian Frezza and Hiromasa Fujii and Fuster, {Mark M} and Daniele Generali and Georgakilas, {Alexandros G} and Frank Gieseler and Michael Gilbertson and Green, {Michelle F} and Brendan Grue and Gunjan Guha and Dorota Halicka and Helferich, {William G} and Petr Heneberg and Patricia Hentosh and Hirschey, {Matthew D} and Hofseth, {Lorne J} and Holcombe, {Randall F} and Kanya Honoki and Hsue-Yin Hsu and Huang, {Gloria S} and Jensen, {Lasse D} and Jiang, {Wen G} and Jones, {Lee W} and Karpowicz, {Phillip A} and Keith, {W Nicol} and Kerkar, {Sid P} and Khan, {Gazala N} and Mahin Khatami and Ko, {Young H} and Omer Kucuk and Kulathinal, {Rob J} and Kumar, {Nagi B} and Kwon, {Byoung S} and Anne Le and Lea, {Michael A} and Ho-Young Lee and Terry Lichtor and Liang-Tzung Lin and Locasale, {Jason W} and Lokeshwar, {Bal L} and Longo, {Valter D} and Lyssiotis, {Costas A} and MacKenzie, {Karen L} and Meenakshi Malhotra and Maria Marino and Martinez-Chantar, {Maria L} and Ander Matheu and Christopher Maxwell and Eoin McDonnell and Meeker, {Alan K} and Mahya Mehrmohamadi and Kapil Mehta and Michelotti, {Gregory A} and Mohammad, {Ramzi M} and Mohammed, {Sulma I} and Morre, {D James} and Vinayak Muralidhar and Irfana Muqbil and Murphy, {Michael P} and Nagaraju, {Ganji Purnachandra} and Rita Nahta and Elena Niccolai and Somaira Nowsheen and Carolina Panis and Francesco Pantano and Parslow, {Virginia R} and Graham Pawelec and Pedersen, {Peter L} and Brad Poore and Deepak Poudyal and Satya Prakash and Mark Prince and Lizzia Raffaghello and Rathmell, {Jeffrey C} and Rathmell, {W Kimryn} and Ray, {Swapan K} and J{\"o}rg Reichrath and Sarallah Rezazadeh and Domenico Ribatti and Luigi Ricciardiello and Robey, {R Brooks} and Francis Rodier and Rupasinghe, {H P Vasantha} and Russo, {Gian Luigi} and Ryan, {Elizabeth P} and Samadi, {Abbas K} and Isidro Sanchez-Garcia and Sanders, {Andrew J} and Daniele Santini and Malancha Sarkar and Tetsuro Sasada and Saxena, {Neeraj K} and Shackelford, {Rodney E} and {Shantha Kumara}, {H M C} and Dipali Sharma and Shin, {Dong M} and David Sidransky and Siegelin, {Markus David} and Emanuela Signori and Neetu Singh and Sharanya Sivanand and Daniel Sliva and Carl Smythe and Carmela Spagnuolo and Stafforini, {Diana M} and John Stagg and Subbarayan, {Pochi R} and Tabetha Sundin and Talib, {Wamidh H} and Thompson, {Sarah K} and Tran, {Phuoc T} and Hendrik Ungefroren and {Vander Heiden}, {Matthew G} and Vasundara Venkateswaran and Vinay, {Dass S} and Vlachostergios, {Panagiotis J} and Zongwei Wang and Wellen, {Kathryn E} and Whelan, {Richard L} and Yang, {Eddy S} and Huanjie Yang and Xujuan Yang and Paul Yaswen and Clement Yedjou and Xin Yin and Jiyue Zhu and Massimo Zollo",
note = "Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division Copyright {\circledC} 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.",
year = "2015",
month = "12",
doi = "10.1016/j.semcancer.2015.09.007",
language = "English",
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pages = "S276--S304",
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TY - JOUR

T1 - Designing a broad-spectrum integrative approach for cancer prevention and treatment

AU - Block, Keith I

AU - Gyllenhaal, Charlotte

AU - Lowe, Leroy

AU - Amedei, Amedeo

AU - Amin, A R M Ruhul

AU - Amin, Amr

AU - Aquilano, Katia

AU - Arbiser, Jack

AU - Arreola, Alexandra

AU - Arzumanyan, Alla

AU - Ashraf, S Salman

AU - Azmi, Asfar S

AU - Benencia, Fabian

AU - Bhakta, Dipita

AU - Bilsland, Alan

AU - Bishayee, Anupam

AU - Blain, Stacy W

AU - Block, Penny B

AU - Boosani, Chandra S

AU - Carey, Thomas E

AU - Carnero, Amancio

AU - Carotenuto, Marianeve

AU - Casey, Stephanie C

AU - Chakrabarti, Mrinmay

AU - Chaturvedi, Rupesh

AU - Chen, Georgia Zhuo

AU - Chen, Helen

AU - Chen, Sophie

AU - Chen, Yi Charlie

AU - Choi, Beom K

AU - Ciriolo, Maria Rosa

AU - Coley, Helen M

AU - Collins, Andrew R

AU - Connell, Marisa

AU - Crawford, Sarah

AU - Curran, Colleen S

AU - Dabrosin, Charlotta

AU - Damia, Giovanna

AU - Dasgupta, Santanu

AU - DeBerardinis, Ralph J

AU - Decker, William K

AU - Dhawan, Punita

AU - Diehl, Anna Mae E

AU - Dong, Jin-Tang

AU - Dou, Q Ping

AU - Drew, Janice E

AU - Elkord, Eyad

AU - El-Rayes, Bassel

AU - Feitelson, Mark A

AU - Felsher, Dean W

AU - Ferguson, Lynnette R

AU - Fimognari, Carmela

AU - Firestone, Gary L

AU - Frezza, Christian

AU - Fujii, Hiromasa

AU - Fuster, Mark M

AU - Generali, Daniele

AU - Georgakilas, Alexandros G

AU - Gieseler, Frank

AU - Gilbertson, Michael

AU - Green, Michelle F

AU - Grue, Brendan

AU - Guha, Gunjan

AU - Halicka, Dorota

AU - Helferich, William G

AU - Heneberg, Petr

AU - Hentosh, Patricia

AU - Hirschey, Matthew D

AU - Hofseth, Lorne J

AU - Holcombe, Randall F

AU - Honoki, Kanya

AU - Hsu, Hsue-Yin

AU - Huang, Gloria S

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N1 - Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2015/12

Y1 - 2015/12

N2 - 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.

AB - 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.

KW - multi-targeted

KW - cancer hallmarks

KW - phytochemicals

KW - targeted therapy

KW - integrative medicine

U2 - 10.1016/j.semcancer.2015.09.007

DO - 10.1016/j.semcancer.2015.09.007

M3 - Article

VL - 35

SP - S276-S304

JO - Seminars in cancer biology

JF - Seminars in cancer biology

SN - 1044-579X

IS - Supplement

ER -