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 language | English (US) |
|---|---|
| Pages (from-to) | S276-S304 |
| Journal | Seminars in Cancer Biology |
| Volume | 35 |
| DOIs | |
| State | Published - 2015 |
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Keywords
- Cancer hallmarks
- Integrative medicine
- Multi-targeted
- Phytochemicals
- Targeted therapy
ASJC Scopus subject areas
- Cancer Research
Cite this
Designing a broad-spectrum integrative approach for cancer prevention and treatment. / Block, Keith I.; Gyllenhaal, Charlotte; Lowe, Leroy; Amedei, Amedeo; Ruhul Amin, A. R M; Amin, Amr; Aquilano, Katia; Arbiser, Jack; Arreola, Alexandra; Arzumanyan, Alla; Salman Ashraf, S.; 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; Drewa, Janice E.; Elkord, Eyad; El-Rayes, Bassel; Feitelson, Mark A.; Felsheru, 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; Guhal, 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.; Leb, Anne; Leab, 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; Maxwellx, Christopher; McDonnell, Eoin; Meeker, Alan K.; Mehrmohamadi, Mahya; Mehta, Kapil; Michelotti, Gregory A.; Mohammad, Ramzi M.; Mohammed, Sulma I.; Morre, D. James; Muqbil, Irfana; Muralidharcq, Vinayak; 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; Robeydf, R. Brooks; Rodierdh, 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, 2015, p. S276-S304.Research output: Contribution to journal › Article
}
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 - Ruhul Amin, A. R M
AU - Amin, Amr
AU - Aquilano, Katia
AU - Arbiser, Jack
AU - Arreola, Alexandra
AU - Arzumanyan, Alla
AU - Salman Ashraf, S.
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 - Drewa, Janice E.
AU - Elkord, Eyad
AU - El-Rayes, Bassel
AU - Feitelson, Mark A.
AU - Felsheru, 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 - Guhal, 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.
AU - Jensen, Lasse D.
AU - Jiang, Wen G.
AU - Jones, Lee W.
AU - Karpowicz, Phillip A.
AU - Keith, W. Nicol
AU - Kerkar, Sid P.
AU - Khan, Gazala N.
AU - Khatami, Mahin
AU - Ko, Young H.
AU - Kucuk, Omer
AU - Kulathinal, Rob J.
AU - Kumar, Nagi B.
AU - Kwon, Byoung S.
AU - Leb, Anne
AU - Leab, Michael A.
AU - Lee, Ho Young
AU - Lichtor, Terry
AU - Lin, Liang Tzung
AU - Locasale, Jason W.
AU - Lokeshwar, Bal L.
AU - Longo, Valter D.
AU - Lyssiotis, Costas A.
AU - MacKenzie, Karen L.
AU - Malhotra, Meenakshi
AU - Marino, Maria
AU - Martinez-Chantar, Maria L.
AU - Matheu, Ander
AU - Maxwellx, Christopher
AU - McDonnell, Eoin
AU - Meeker, Alan K.
AU - Mehrmohamadi, Mahya
AU - Mehta, Kapil
AU - Michelotti, Gregory A.
AU - Mohammad, Ramzi M.
AU - Mohammed, Sulma I.
AU - Morre, D. James
AU - Muqbil, Irfana
AU - Muralidharcq, Vinayak
AU - Murphy, Michael P.
AU - Nagaraju, Ganji Purnachandra
AU - Nahta, Rita
AU - Niccolai, Elena
AU - Nowsheen, Somaira
AU - Panis, Carolina
AU - Pantano, Francesco
AU - Parslow, Virginia R.
AU - Pawelec, Graham
AU - Pedersen, Peter L.
AU - Poore, Brad
AU - Poudyal, Deepak
AU - Prakash, Satya
AU - Prince, Mark
AU - Raffaghello, Lizzia
AU - Rathmell, Jeffrey C.
AU - Rathmell, W. Kimryn
AU - Ray, Swapan K.
AU - Reichrath, Jörg
AU - Rezazadeh, Sarallah
AU - Ribatti, Domenico
AU - Ricciardiello, Luigi
AU - Robeydf, R. Brooks
AU - Rodierdh, Francis
AU - Rupasinghe, H. P Vasantha
AU - Russo, Gian Luigi
AU - Ryan, Elizabeth P.
AU - Samadi, Abbas K.
AU - Sanchez-Garcia, Isidro
AU - Sanders, Andrew J.
AU - Santini, Daniele
AU - Sarkar, Malancha
AU - Sasada, Tetsuro
AU - Saxena, Neeraj K.
AU - Shackelford, Rodney E.
AU - Shantha Kumara, H. M C
AU - Sharma, Dipali
AU - Shin, Dong M.
AU - Sidransky, David
AU - Siegelin, Markus David
AU - Signori, Emanuela
AU - Singh, Neetu
AU - Sivanand, Sharanya
AU - Sliva, Daniel
AU - Smythe, Carl
AU - Spagnuolo, Carmela
AU - Stafforini, Diana M.
AU - Stagg, John
AU - Subbarayan, Pochi R.
AU - Sundin, Tabetha
AU - Talib, Wamidh H.
AU - Thompson, Sarah K.
AU - Tran, Phuoc T.
AU - Ungefroren, Hendrik
AU - Vander Heiden, Matthew G.
AU - Venkateswaran, Vasundara
AU - Vinay, Dass S.
AU - Vlachostergios, Panagiotis J.
AU - Wang, Zongwei
AU - Wellen, Kathryn E.
AU - Whelan, Richard L.
AU - Yang, Eddy S.
AU - Yang, Huanjie
AU - Yang, Xujuan
AU - Yaswen, Paul
AU - Yedjou, Clement
AU - Yin, Xin
AU - Zhu, Jiyue
AU - Zollo, Massimo
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Cancer hallmarks
KW - Integrative medicine
KW - Multi-targeted
KW - Phytochemicals
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=84952918579&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952918579&partnerID=8YFLogxK
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
ER -