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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.
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. - ISSN 1044-579X. - STAMPA. - 35:Supplement(2015), pp. S276-S304. [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
2015
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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/536029
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Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
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