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16 results on '"Elkord, Eyad"'

1. What is the relevance of FoxP3 in the tumor microenvironment and cancer outcomes?

Author

Meyiah, Abdo and Elkord, Eyad

Subjects
TUMOR microenvironment, CANCER prognosis, TRANSCRIPTION factors, CANCER invasiveness, REGULATORY T cells
Abstract

Forkhead box P3 (FoxP3) transcription factor plays critical roles in controlling immune responses and cancer progression in different cancers. FoxP3 expression within the tumor microenvironment (TME) may influence clinical outcomes negatively or positively, and it could play dual roles in cancer, either by promoting or inhibiting tumor development and progression. Some studies reported that high levels of FoxP3 could be associated with tumor progression and worse prognosis, while others reported contradictory results. In this special report, we present a brief account on the role and function of FoxP3 in the TME, and its contribution to the clinical outcomes of cancer patients. Importantly, we give insights on the potential factors that could contribute to different clinical outcomes in cancer patients. Different studies showed that FoxP3 expression can be associated with bad prognoses in cancer patients. However, FoxP3 could have opposing roles by enhancing cancer progression or regression. Location and expression of FoxP3 in T cells or tumor cells can have different impacts on cancer prognoses. Different factors should be considered to establish FoxP3 as a more robust prognostic biomarker and a potential therapeutic target for enhancing anti-tumor immunity and improving clinical outcomes of cancer patients. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Designing a broad-spectrum integrative approach for cancer prevention and treatment

Author

Block, Keith I, Gyllenhaal, Charlotte, Lowe, Leroy, Amedei, Amedeo, Amin, ARM 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, and Matheu, Ander

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Rare Diseases, Precision Medicine, Aetiology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Good Health and Well Being, Antineoplastic Agents, Phytogenic, Drug Resistance, Neoplasm, Genetic Heterogeneity, Humans, Molecular Targeted Therapy, Neoplasms, Signal Transduction, Tumor Microenvironment, Multi-targeted, Cancer hallmarks, Phytochemicals, Targeted therapy, Integrative medicine, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
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.

Published
2015

4. FoxP3+ T regulatory cells in cancer: Prognostic biomarkers and therapeutic targets.

Author

Saleh, Reem and Elkord, Eyad

Subjects
*IMMUNOTHERAPY, *SUPPRESSOR cells, *IMMUNE checkpoint inhibitors, *CANCER cells, *FORKHEAD transcription factors, *T cells, *CANCER cell growth, *PROTEINS, *IMMUNOLOGICAL tolerance, *RESEARCH, *ANIMAL experimentation, *RESEARCH methodology, *CELL physiology, *PROGNOSIS, *EVALUATION research, *MEDICAL cooperation, *COMPARATIVE studies, *TUMORS
Abstract

T Regulatory cells (Tregs) can have both protective and pathological roles. They maintain immune homeostasis and inhibit immune responses in various diseases, including cancer. Proportions of Tregs in the peripheral blood of some cancer patients increase by approximately two-fold, compared to those in healthy individuals. Tregs contribute to cancer development and progression by suppressing T effector cell functions, thereby compromising tumor killing and promoting tumor growth. Highly immunosuppressive Tregs express upregulated levels of the transcription factor, Forkhead box protein P3 (FoxP3). Elevated levels of FoxP3+ Tregs within the tumor microenvironment (TME) showed a positive correlation with poor prognosis in various cancer patients. Despite the success of immunotherapy, including the use of immune checkpoint inhibitors, a significant proportion of patients show low response rates as a result of primary or acquired resistance against therapy. Some of the mechanisms which underlie the development of therapy resistance are associated with Treg suppressive function. In this review, we describe Treg contribution to cancer development/progression, and the mechanisms of Treg-mediated immunosuppression. We discuss the prognostic significance of FoxP3+ Tregs in different cancers and their potential use as prognostic biomarkers. We also describe potential therapeutic strategies to target Tregs in combination with other types of immunotherapies aiming to overcome tumor resistance and improve clinical outcomes in cancer patients. Overall, understanding the prognostic significance of FoxP3+ Tregs in various cancers and their contribution to therapy resistance could help in the development of more effective targeted therapeutic strategies to enhance the clinical outcomes in cancer patients. [ABSTRACT FROM AUTHOR]

Published
2020
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5. T regulatory cells in cancer

Author

Elkord Eyad

Subjects
Cancer stem cell, business.industry, Immunology, Cancer research, medicine, Cancer, Immunology and Allergy, medicine.disease, business
Published
2013
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6. Therapeutic prospects of targeting myeloid‐derived suppressor cells and immune checkpoints in cancer.

Author

Toor, Salman M and Elkord, Eyad

Subjects
*THERAPEUTICS, *INTERLEUKIN-6, *SUPPRESSOR cells, *T cells, *IMMUNOTHERAPY, *CANCER
Abstract

Immune evasion is a characteristic of most human malignancies and is induced via various mechanisms. Immunosuppressive cells, including myeloid‐derived suppressor cells (MDSC) and regulatory T cells (Treg), are key mediators in assisting tumors to escape immune surveillance. Expansion of MDSC, Treg and elevated levels of immune checkpoints (IC) are frequently detected in the tumor microenvironment and periphery of cancer patients. Various therapeutic agents have been shown to target MDSC and to block IC for inducing anti‐tumor immunity and reversal of tumor immune escape. Importantly, some recent studies have shown that MDSC targeting improves the efficacy of IC blockade in cancer therapy. However, there is a pressing need to improve our understanding of the distinct role of these cells to develop combination therapy that attacks tumor cells from all frontiers to improve cancer therapeutics. Herein, we discuss the role of MDSC in cancer progression, interactions with IC in the context of anti‐cancer immunity and the current therapeutic strategies to target MDSC and block IC in cancer. Expansion of MDSC, Treg and elevated expression levels of immune checkpoints (IC) are frequently detected in the tumor microenvironment and periphery of cancer patients. Recent studies have shown that MDSC targeting improves the efficacy of IC blockade in cancer therapy. Herein, we discuss the role of MDSC in cancer progression, interactions with IC and the current therapeutic strategies to target MDSC and block IC in cancer. [ABSTRACT FROM AUTHOR]

Published
2018
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7. Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells.

Author

Sasidharan Nair, Varun and Elkord, Eyad

Abstract

Abstract: Regulatory T cells (Tregs) play essential roles in immune homeostasis; however, their role in tumor microenvironment (TME) is not completely evident. Several studies reported that infiltration of Tregs into various tumor tissues promotes tumor progression by limiting antitumor immunity and supporting tumor immune evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells expressing different immunosuppressive molecules favoring tumor progression. For an effective cancer therapy, it is critical to understand the Treg heterogeneity and biology in the TME. Recent studies have shown that immune checkpoint molecules promote cancer progression through various antitumor inhibitory mechanisms. Recent advances in cancer immunotherapy have shown the promising potentials of immune checkpoint inhibitors (ICIs) in inducing antitumor immune responses and clinical benefits in patients with cancer at late stages. Most studies revealed the effect of ICIs on T effector cells, and little is known about their effect on Tregs. In this review, we highlight the effects of the ICIs, including anti‐CTLA‐4, anti‐PD‐1/PD‐L1, anti‐LAG‐3, anti‐TIM‐3, and anti‐TIGIT, on tumor‐infiltrating and peripheral Tregs to elicit effector T‐cell functions against tumors. Additionally, we discuss how ICIs may target Tregs for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2018
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8. Editorial: CD4+ T Cells in Cancer Immunotherapies.

Author

González-Navajas, José M., Elkord, Eyad, and Lee, Jongdae

Subjects
T cells, CANCER cells, REGULATORY T cells, PSYCHONEUROIMMUNOLOGY, T helper cells, IMMUNE checkpoint inhibitors
Abstract

Among the different immunotherapy approaches, immune checkpoint inhibition (ICI) therapy and chimeric antigen receptor (CAR) T cells have arguably shown the greatest potential. Keywords: CD4; immunotherapy; immune checkpoint inhibitor (ICI); cancer; T lymphocyte EN CD4 immunotherapy immune checkpoint inhibitor (ICI) cancer T lymphocyte 1 2 2 09/08/21 20210906 NES 210906 In the last 20 years, remarkable advances in the field of immunotherapy have led to new therapeutic options for patients with a wide range of cancer types. [Extracted from the article]

Published
2021
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9. Myeloid-derived suppressor cells in cancer: recent progress and prospects.

Author

Khaled, Yazan S, Ammori, Basil J, and Elkord, Eyad

Subjects
SUPPRESSOR cells, IMMUNOSUPPRESSIVE agents, CANCER treatment, IMMUNOTHERAPY, IMMUNE response
Abstract

Immunosuppressive cells, mainly myeloid-derived suppressor cells (MDSCs) and T regulatory cells, downregulate antitumour immunity and cancer immunotherapy. MDSCs are a heterogeneous group of immature myeloid cells that negatively regulate the immune responses during tumour progression, inflammation and infection. Whilst there have been extensive laboratory investigations aimed at characterising the MDSC subsets in cancer, there remains a significant gap in our understanding of their phenotypical and functional heterogeneity. In this article, we review data concerning the phenotypical and functional role of MDSCs in cancers. Importantly, we analyse the value of MDSCs as a prognostic factor in various clinical settings and the possible therapeutic approaches towards elimination of their immunosuppressive activity and enhancement of beneficial antitumour immune responses. MDSCs promote tumour immune evasion by inhibiting T-cell responses, as well as by supporting tumour progression. Accumulation of MDSCs is associated with the progression of human cancers, and their elimination was shown to improve anti-tumour immune responses. Phenotypical characterisation of MDSCs has been poorly investigated in many human cancers and lacks comprehensive clinicopathological correlation data. Although the need for effective therapeutic agents to eliminate the MDSC suppressive effect is immense, their role has been examined only in a few clinical settings. [ABSTRACT FROM AUTHOR]

Published
2013
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10. Macrophage Inhibitory Cytokine-1: A review of its pleiotropic actions in cancer.

Author

Khaled, Yazan S., Elkord, Eyad, and Ammori, Basil J.

Subjects
*CANCER treatment, *CYTOKINES, *MACROPHAGES, *BIOMARKERS, *CYCLOOXYGENASE inhibitors, *APPETITE loss, *COLON cancer
Abstract

Background and aims: The macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-β (TGF-β) superfamily that can serve as a potential immune-therapeutic target and/or a prognostic biomarker for the treatment of some cancers. This article reviews the current published data on the molecular and clinical application of MIC-1 in cancer. Methods: Literature review was conducted using Medline, PubMed, Embase and Cochrane databases. Results: MIC-1 is the only known secreted p53-regulated cytokine and therefore can serve as a biomarker for p53 activation both in vitro and in vivo. MIC-1 gene can be activated by cyclooxygenase inhibitors and has pro-apoptotic and anti-tumour activities. Although MIC-1 may induce anti-tumour role in the early stages of cancer, it can promote the invasiveness and metastatic behaviour in advanced stages. Greater concentration of MIC-1 was associated with the induction of cancer-related anorexia and weight loss in animals and humans. Of clinical interest, MIC-1 out-performs all available biomarkers including CA19-9 in the differentiation of patients with resectable pancreatic cancer from patients with benign pancreatic disease. MIC-1 gene was over-expressed in colorectal cancer (CRC), and a progressive rise of MIC-1 serum levels was noted in patients with adenomatous polyps and further in patients with CRC. Conclusions: MIC-1 cytokine has the potential characteristics for a new diagnostic biomarker and a target for cancer treatment. Further research however is required to characterise MIC-1 receptors and to revalidate its diagnostic power in larger and better-standardised clinical studies. [ABSTRACT FROM AUTHOR]

Published
2012
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11. CD4+ T-cell recognition of human 5T4 oncofoetal antigen: implications for initial depletion of CD25+ T cells.

Author

Elkord, Eyad, Burt, Deborah J., Drijfhout, Jan W., Hawkins, Robert E., and Stern, Peter L.

Subjects
*CARCINOEMBRYONIC antigen, *DENDRITIC cells, *T cells, *LYMPHOCYTES, *CANCER
Abstract

The human 5T4 (h5T4) oncofoetal antigen is expressed by a wide variety of human carcinomas including colorectal, ovarian, gastric and renal, but rarely on normal tissues. Its restricted expression on tumour tissues as well as its association with tumour progression and bad prognosis has driven the development of a MVA-based vaccine (TroVax) which has been tested in several early phase clinical trials and these studies have led to the start of a phase III trial in renal cell carcinoma patients. We have recently shown that CD8+ T cells recognizing h5T4 can be generated in the absence of CD4+ T cells from peripheral blood lymphocytes of human healthy individuals. We report the existence and expansion of human CD4+ T cells against h5T4 by stimulation with autologous monocyte-derived dendritic cells infected with a replication defective adenovirus encoding the h5T4 cDNA (Ad-h5T4). The h5T4-specific T-cell responses in normal individuals are enhanced by initial depletion of CD25+ cells (putative T regulatory cells) prior to the in vitro stimulation. We have identified a novel h5T4-derived 15-mer peptide recognized by CD4+ T cells in HLA-DR4 positive healthy individuals. Interestingly, CD4+ T cells spontaneously recognizing a different 5T4 epitope restricted by HLA-DR were identified in tumour-infiltrating lymphocytes isolated from a regressing renal cell carcinoma lung metastasis. Our data show that CD4+ T cells recognizing h5T4 can be expanded and detected in healthy individuals and a renal cell carcinoma patient. Such h5T4-specific CD4+ T cells boosted or induced by vaccination could act to modulate both cell or antibody mediated anti-tumour responses. [ABSTRACT FROM AUTHOR]

Published
2008
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12. Thymus-derived, peripherally derived, and in vitro-induced T regulatory cells.

Author

Elkord, Eyad

Subjects
EPIGENETICS, ENZYME induction, PHENOTYPES
Abstract

An introduction is presented in which the editor discusses various reports within the issue on topics including progress of epigenetic modifications, molecular signatures and induction process, and reviews on phenotypic and functional differences between tTregs and pTreg subsets.

Published
2014
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15. Designing a broad-spectrum integrative approach for cancer prevention and treatment

Author

Chandra S. Boosani, William K. Decker, Punita Dhawan, Georgia Zhuo Chen, Mark E. Prince, Balakrishna L. Lokeshwar, Nagi B. Kumar, Michelle F. Green, Alan Bilsland, Michael P. Murphy, Dong M. Shin, H.P. Vasantha Rupasinghe, Paul Yaswen, Anupam Bishayee, Christian Frezza, John Stagg, Mahin Khatami, Lynnette R. Ferguson, R. Brooks Robeydf, Kanya Honoki, Alan K. Meeker, A.R.M. Ruhul Amin, Huanjie Yang, Eoin McDonnell, Virginia R. Parslow, Phuoc T. Tran, Patricia Hentosh, Frank Gieseler, Gloria S. Huang, Sulma I. Mohammed, Ho Young Lee, Giovanna Damia, Alexandra Arreola, Wamidh H. Talib, Mark A. Feitelson, Luigi Ricciardiello, Massimo Zollo, Sarallah Rezazadeh, Diana M. Stafforini, Katia Aquilano, Phillip Karpowicz, Markus D. Siegelin, Neetu Singh, Alexandros G. Georgakilas, Domenico Ribatti, Neeraj K. Saxena, Carl Smythe, Beom K. Choi, Mark M. Fuster, Gian Luigi Russo, Amedeo Amedei, Anna Mae Diehl, Terry Lichtor, D. James Morré, Charlotte Gyllenhaal, Vasundara Venkateswaran, Colleen S. Curran, Ramzi M. Mohammad, Jiyue Zhu, Anne Leb, Lizzia Raffaghello, Fabian Benencia, Sid P. Kerkar, Eddy S. Yang, Wen Guo Jiang, Jason W. Locasale, Alla Arzumanyan, W. Nicol Keith, Dorota Halicka, Gunjan Guhal, Xin Yin, Helen Chen, Irfana Muqbil, Gary L. Firestone, Panagiotis J. Vlachostergios, Maria Marino, Meenakshi Malhotra, Stacy W. Blain, Amancio Carnero, Liang Tzung Lin, Dass S. Vinay, Satya Prakash, Hsue-Yin Hsu, María L. Martínez-Chantar, Daniele Generali, Jeffrey C. Rathmell, Karen L. MacKenzie, Valter D. Longo, Dipita Bhakta, Ralph J. DeBerardinis, S. Salman Ashraf, Elena Niccolai, Hendrik Ungefroren, Carmela Fimognari, Mahya Mehrmohamadi, Zongwei Wang, Clement G. Yedjou, Costas A. Lyssiotis, Lasse Jensen, Jörg Reichrath, Sarah K. Thompson, Rita Nahta, David Sidransky, Q. Ping Dou, Brendan Grue, Isidro Sánchez-García, Brad Poore, Helen M. Coley, Bassel F. El-Rayes, Sophie Chen, Randall F. Holcombe, Dipali Sharma, Mrinmay Chakrabarti, Asfar S. Azmi, William G. Helferich, Gregory A. Michelotti, H. M. C. Shantha Kumara, Petr Heneberg, Rodney E. Shackelford, Andrew James Sanders, Daniel Sliva, Swapan K. Ray, Omer Kucuk, Christopher Maxwellx, Abbas Samadi, Leroy Lowe, Sarah Crawford, Daniele Santini, Andrew Collins, Yi Charlie Chen, Santanu Dasgupta, Kathryn E. Wellen, Richard L. Whelan, Janice E. Drewa, Ander Matheu, Sharanya Sivanand, Tetsuro Sasada, Xujuan Yang, Lee W. Jones, Byoung S. Kwon, Amr Amin, Francis Rodierdh, Ganji Purnachandra Nagaraju, Charlotta Dabrosin, Graham Pawelec, Rob J. Kulathinal, Elizabeth P. Ryan, Hiromasa Fujii, Thomas E. Carey, Somaira Nowsheen, Young Hee Ko, Deepak Poudyal, Eyad Elkord, Emanuela Signori, Rupesh Chaturvedi, Peter L. Pedersen, Carmela Spagnuolo, Keith I. Block, Marianeve Carotenuto, Vinayak Muralidharcq, Stephanie C. Casey, Kapil Mehta, Tabetha Sundin, Dean W. Felsheru, Matthew D. Hirschey, Matthew G. Vander Heiden, Lorne J. Hofseth, Francesco Pantano, Maria Rosa Ciriolo, Michael A. Leab, Carolina Panis, Marisa Connell, Gazala Khan, W. Kimryn Rathmell, Malancha Sarkar, Michael Gilbertson, Jack L. Arbiser, Penny B. Block, Pochi R. Subbarayan, Jin-Tang Dong, Frezza, Christian [0000-0002-3293-7397], Murphy, Mike [0000-0003-1115-9618], Apollo - University of Cambridge Repository, National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Andalucía, Associazione Italiana per la Ricerca sul Cancro, Avon Foundation for Women, Junta de Castilla y León, Ministerio de Ciencia e Innovación (España), Federal Ministry of Education and Research (Germany), Canadian Institutes of Health Research, Ikerbasque Basque Foundation for Science, American Cancer Society, European Commission, Swedish Research Council, University of Glasgow, 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. Jame, 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. Brook, Rodier, Franci, 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, Amin, A R M Ruhul, Ashraf, S Salman, Dong, Jin-Tang, Dou, Q Ping, El-Rayes, Bassel, Hsu, Hsue-Yin, Keith, W Nicol, Lee, Ho-Young, Lin, Liang-Tzung, Martinez-Chantar, Maria L, Morre, D Jame, Rathmell, W Kimryn, Robey, R Brook, Rupasinghe, H P Vasantha, Sanchez-Garcia, Isidro, Shantha Kumara, H M C, Block, Ki, Gyllenhaal, C, Lowe, L, Amedei, A, Amin, Ar, Amin, A, Aquilano, K, Arbiser, J, Arreola, A, Arzumanyan, A, Ashraf, S, Azmi, A, Benencia, F, Bhakta, D, Bilsland, A, Bishayee, A, Blain, Sw, Block, Pb, Boosani, C, Carey, Te, Carnero, A, 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, C, Dabrosin, C, Damia, G, Dasgupta, S, Deberardinis, Rj, Decker, Wk, Dhawan, P, Diehl, Am, Dong, Jt, 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, Hy, Huang, G, 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, B, Le, A, Lea, Ma, Lee, Hy, Lichtor, T, Lin, Lt, 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, Hp, Russo, Gl, Ryan, Ep, Samadi, Ak, Sanchez Garcia, I, Sanders, Aj, Santini, D, Sarkar, M, Sasada, T, Saxena, Nk, Shackelford, Re, Shantha Kumara, Hm, 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, D, Vlachostergios, Pj, Wang, Z, Wellen, Ke, Whelan, Rl, Yang, E, Yang, H, Yang, X, Yaswen, P, Yedjou, C, Yin, X, Zhu, J, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G., Ruhul Amin, A. R. M., Salman Ashraf, S., Azmi, Asfar S., Blain, Stacy W., Block, Penny B., Boosani, Chandra S., Carey, Thomas E., Casey, Stephanie C., Choi, Beom K., Coley, Helen M., Collins, Andrew R., Curran, Colleen S., Deberardinis, Ralph J., Decker, William K., Diehl, Anna Mae E., Drewa, Janice E., Feitelson, Mark A., Felsheru, Dean W., Ferguson, Lynnette R., Firestone, Gary L., Fuster, Mark M., Georgakilas, Alexandros G., Green, Michelle F., Guhal, Gunjan, Helferich, William G., Hirschey, Matthew D., Hofseth, Lorne J., Holcombe, Randall F., Huang, Gloria S., Jensen, Lasse D., Jiang, Wen G., Jones, Lee W., Karpowicz, Phillip A., Kerkar, Sid P., Khan, Gazala N., Ko, Young H., Kulathinal, Rob J., Kumar, Nagi B., Kwon, Byoung S., Leb, Anne, Leab, Michael A., Locasale, Jason W., Lokeshwar, Bal L., Longo, Valter D., Lyssiotis, Costas A., Maxwellx, Christopher, Meeker, Alan K., Michelotti, Gregory A., Mohammad, Ramzi M., Mohammed, Sulma I., Muralidharcq, Vinayak, Murphy, Michael P., Parslow, Virginia R., Pedersen, Peter L., Rathmell, Jeffrey C., Ray, Swapan K., Robeydf, R. Brook, Rodierdh, Franci, Ryan, Elizabeth P., Samadi, Abbas K., Sanders, Andrew J., Saxena, Neeraj K., Shackelford, Rodney E., Shantha Kumara, H. M. C., Shin, Dong M., Stafforini, Diana M., Subbarayan, Pochi R., Talib, Wamidh H., Thompson, Sarah K., Tran, Phuoc T., Vinay, Dass S., Vlachostergios, Panagiotis J., Wellen, Kathryn E., Whelan, Richard L., and Yang, Eddy S.

Subjects
Cancer Research, medicine.medical_treatment, Phytochemicals, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Pharmacology, Bioinformatics, Targeted therapy, Broad spectrum, 0302 clinical medicine, Cancer hallmark, Neoplasms, Tumor Microenvironment, Molecular Targeted Therapy, Precision Medicine, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Cancer hallmarks, Integrative medicine, Multi-targeted, 1. No poverty, Life Sciences, 3. Good health, 030220 oncology & carcinogenesis, Signal Transduction, Phytochemical, Article, RC0254, 03 medical and health sciences, Therapeutic approach, Genetic Heterogeneity, medicine, Humans, Settore BIO/10, Biology, 030304 developmental biology, Tumor microenvironment, Cancer och onkologi, Cancer prevention, business.industry, Cancer, Precision medicine, medicine.disease, Antineoplastic Agents, Phytogenic, Drug Resistance, Neoplasm, Data_GENERAL, Cancer and Oncology, business
Abstract

Under a Creative Commons license.-- Review.-- et al., 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., Amr Amin was funded by Terry Fox Foundation Grant # TF-13-20 and UAEU Program for Advanced Research (UPAR) #31S118; Jack Arbiser was funded by NIHAR47901; Alexandra Arreola was funded by NIH NRSA Grant F31CA154080; Alla Arzumanyan was funded by NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer (AI076535); Work in the lab of Asfar S. Azmi is supported by NIH R21CA188818 as well as from Sky Foundation Inc. Michigan; Fabian Benencia was supported by NIH Grant R15 CA137499-01; Alan Bilsland was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Amancio Carnero was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-6844 and CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012). His work on this project has also been made possible thanks to the Grant PIE13/0004 co-funded by the ISCIII and FEDER funds; Stephanie C. Casey was supported by NIH Grant F32CA177139; Mrinmay Chakrabarti was supported by the United Soybean Board; Rupesh Chaturvedi was supported by an NIH NCCAM Grant (K01AT007324); Georgia Zhuo Chen was supported by an NIH NCI Grant (R33 CA161873-02); Helen Chen acknowledges financial support from the Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Sophie Chen acknowledges financial support from the Ovarian and Prostate Cancer Research Trust, UK; Yi Charlie Chen acknowledges financial support from the West Virginia Higher Education Policy Commission/Division of Science Research, his research was also supported by NIH grants (P20RR016477 and P20GM103434) from the National Institutes of Health awarded to the West Virginia IDeA Network of Biomedical Research Excellence; Maria Rosa Ciriolo was partially supported by the Italian Association for Cancer Research (AIRC) Grants #IG10636 and #15403; Helen M. Coley acknowledges financial support from the GRACE Charity, UK and the Breast Cancer Campaign, UK; Marisa Connell was supported by a Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Sarah Crawford was supported by a research grant from Connecticut State University; Charlotta Dabrosin acknowledges financial support from the Swedish Research Council and the Swedish Research Society; Giovanna Damia gratefully acknowledges the generous contributions of The Italian Association for Cancer Research (IG14536 to G.D.), Santanu Dasgupta gratefully acknowledges the support of the University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; William K. Decker was supported in part by CPRIT, the Cancer Prevention and Research Institute of Texas; Anna Mae E. Diehl was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA), Gilead and Shire Pharmaceuticals; Q. Ping Dou was partially supported by NIH/NCI (1R01CA20009, 5R01CA127258-05 and R21CA184788), and NIH P30 CA22453 (to Karmanos Cancer Institute); Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division; Eyad Elkord thanks the National Research Foundation, United Arab Emirates University and the Terry Fox Foundation for supporting research projects in his lab; Bassel El-Rayes was supported by Novartis Pharmaceutical, Aveo Pharmaceutical, Roche, Bristol Myers Squibb, Bayer Pharmaceutical, Pfizer, and Kyowa Kirin; Mark A. Feitelson was supported by NIH/NIAID Grant AI076535, Dean W. Felsher was supported by NIH grants (R01CA170378, U54CA149145, and U54CA143907); Lynnette R Ferguson was financially supported by the Auckland Cancer Society and the Cancer Society of New Zealand; Gary L. Firestone was supported by NIH Public Service Grant CA164095 awarded from the National Cancer Institute; Christian Frezza “would like to acknowledge funding from a Medical Research Council CCU-Program Grant on cancer metabolism, and a unique applicant AICR project grant”; Mark M. Fuster was supported by NIH Grant R01-HL107652; Alexandros G. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program ‘Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES (Grant number MIS 379346) and COST Action CM1201 ‘Biomimetic Radical Chemistry’; Michelle F. Green was supported by a Duke University Molecular Cancer Biology T32 Training Grant; Brendan Grue was supported by a National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Dorota Halicka was supported by by NIH NCI grant NCI RO1 28704; Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, by the Czech Science Foundation projects 15-03834Y and P301/12/1686, by the Czech Health Research Council AZV project 15-32432A, and by the Internal Grant Agency of the Ministry of Health of the Czech Republic project NT13663-3/2012; Matthew D. Hirschey wishes to acknowledge Duke University Institutional Support, the Duke Pepper Older Americans Independence Center (OAIC) Program in Aging Research supported by the National Institute of Aging (P30AG028716-01) and NIH/NCI training grants to Duke University (T32-CA059365-19 and 5T32-CA059365), Lorne J. Hofseth was supported by NIH grants (1R01CA151304, 1R03CA1711326, and 1P01AT003961); Kanya Honoki was supported in part by the grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 24590493); Hsue-Yin Hsu was supported in part by grants from the Ministry of Health and Welfare (CCMP101-RD-031 and CCMP102-RD-112) and Tzu-Chi University (61040055-10) of Taiwan; Lasse D. Jensen was supported by Svenska Sallskapet for Medicinsk Forskning, Gosta Fraenkels Stiftelse, Ak.e Wibergs Stiftelse, Ollie och Elof Ericssons Stiftelse, Linkopings Universitet and the Karolinska Institute, Sweden; Wen G. Jiang wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Lee W. Jones was supported in part by grants from the NIH NCI; W Nicol Keith was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Sid P. Kerkar was supported by the NIH Intramural Research Program; Rob J. Kulathinal was supported by the National Science Foundation, and the American Cancer Society; Byoung S. Kwon was supported in part by National Cancer Center (NCC-1310430-2) and National Research Foundation (NRF-2005-0093837); Anne Le was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, a Lustgarten Fund Grant 90049125 and Grant NIHR21CA169757 (to Anne Le); Michael A. Lea was funded by the The Alma Toorock Memorial for Cancer Research; Ho-Young Lee., This work was supported by grants from the National Research Foundation of Korea (NRF), the Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea (Nos. 2011-0017639 and 2011-0030001) and by a NIH Grant R01 CA100816; Liang-Tzung Lin was supported in part by a grant from the Ministry of Education of Taiwan (TMUTOP103005-4); Jason W. Locasale acknowledges support from NIH awards (CA168997 and AI110613) and the International Life Sciences Institute; Bal L. Lokeshwar was supported in part by United States’ Public Health Services Grants: NIH R01CA156776 and VA-BLR&D Merit Review Grant No. 5I01-BX001517-02; Valter D. Longo acknowledges support from NIH awards (P01AG034906 and R01AG020642) and from the V Foundation; Costas A. Lyssiotis was funded in part by the Pancreatic Cancer Action Network as a Pathway to Leadership Fellow and through a Dale F. Frey Breakthrough award from the Damon Runyon Cancer Research Foundation; Karen L. MacKenzie wishes to acknowledge the support from the Children's Cancer Institute Australia (affiliated with the University of New South Wales, Australia and the Sydney Children's Hospital Network); Maria Marino was supported by grant from University Roma Tre to M.M. (CLA 2013) and by the Italian Association for Cancer Research (AIRC-Grant #IG15221), Ander Matheu is funded by Carlos III Health Institute (AM: CP10/00539), Basque Foundation for Science (IKERBASQUE) and Marie Curie CIG Grant (AM: 2012/712404); Christopher Maxwell was supported by funding from the Canadian Institutes of Health Research, in partnership with the Avon Foundation for Women (OBC-134038) and the Canadian Institutes of Health Research New Investigator Salary Award (MSH-136647); Eoin McDonnell received Duke University Institutional Support; Kapil Mehta was supported by Bayer Healthcare System G4T (Grants4Targets); Gregory A. Michelotti received support from NIH NIDDK, NIH NIAAA, and Shire Pharmaceuticals; Vinayak Muralidhar was supported by the Harvard-MIT Health Sciences and Technology Research Assistantship Award; Elena Niccolai was supported by the Italian Ministry of University and the University of Italy; Virginia R. Parslow gratefully acknowledges the financial support of the Auckland Cancer Society Research Centre (ACSRC); Graham Pawelec was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) Grant number 16SV5536K, and by the European Commission (FP7 259679 “IDEAL”); Peter L. Pedersen was supported by NIH Grant CA-10951; Brad Poore was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, the Lustgarten Fund Grant 90049125, and Grant NIHR21CA169757 (to Anne Le); Satya Prakash was supported by a Canadian Institutes of Health Research Grant (MOP 64308); Lizzia Raffaghello was supported by an NIH Grant (P01AG034906-01A1) and Cinque per Mille dell’IRPEF–Finanziamento della Ricerca Sanitaria; Jeffrey C. Rathmell was supported by an NIH Grant (R01HL108006); Swapan K. Ray was supported by the United Soybean Board; Domenico Ribatti received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under Grant agreement n°278570; Luigi Ricciardiello was supported by the AIRC Investigator Grants 10216 and 13837, and the European Community's Seventh Framework Program FP7/2007–2013 under Grant agreement 311876; Francis Rodier acknowledges the support of the Canadian Institute for Health Research (FR: MOP114962, MOP125857), Fonds de Recherche Québec Santé (FR: 22624), and the Terry Fox Research Institute (FR: 1030), Gian Luigi Russo contributed to this effort while participating in the Fulbright Research Scholar Program 2013–14; Isidro Sanchez-Garcia is partially supported by FEDER and by MICINN (SAF2012-32810), by NIH Grant (R01 CA109335-04A1), by Junta de Castilla y León (BIO/SA06/13) and by the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program). Isidro Sanchez-Garcia's lab is also a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program; Andrew J. Sanders wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Neeraj K. Saxena was supported by grant funding from NIH NIDDK (K01DK077137, R03DK089130); Dipali Sharma was partially funded by NIH NCI grants (R01CA131294, R21 CA155686), the Avon Foundation and a Breast Cancer Research Foundation Grant (90047965); Markus David Siegelin received funding from National Institute of Health, NINDS Grant K08NS083732, and the 2013 AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research, Grant Number 13-20-23-SIEG; Neetu Singh was supported by funds from the Department of Science and Technology (SR/FT/LS-063/2008), New Delhi, India; Carl Smythe was supported by Yorkshire Cancer Research and The Wellcome Trust, UK; Carmela Spagnuolo was supported by funding from Project C.I.S.I.A., act n. 191/2009 from the Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region 2007/2013, objectives 2.1, 2.2; Diana M. Stafforini was supported by grants from the National Cancer Institute (5P01CA073992), IDEA Award W81XWH-12-1-0515 from the Department of Defense, and by the Huntsman Cancer Foundation; John Stagg was supported by the Canadian Institutes of Health Research; Pochi R. Subbarayan was supported by the University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant (CTSI-2013-P03) and SEEDS You Choose Awards; Phuoc T. Tran was funded by the DoD (W81XWH-11-1-0272 and W81XWH-13-1-0182), a Kimmel Translational Science Award (SKF-13-021), an ACS Scholar award (122688-RSG-12-196-01-TBG) and the NIH (R01CA166348); Kathryn E. Wellen receives funding from the National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts, American Diabetes Association, and Elsa U. Pardee Foundation; Huanjie Yang was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011), Paul Yaswen was supported by funding from the United States National Institutes of Health (ES019458) and the California Breast Cancer Research Program (17UB-8708); Clement Yedjou was supported by a grant from the National Institutes of Health (Grant # G1200MD007581), through the RCMI-Center for Environmental Health; Xin Yin was supported by NIH/National Heart, Lung, and Blood Institute Training Grant T32HL098062.; Jiyue Zhu was supported by NIH Grant R01GM071725; Massimo Zollo was supported by the European FP7-TuMIC HEALTH-F2-2008-201662, the Italian Association for Cancer research (AIRC) Grant IG # 11963 and the Regione Campania L.R:N.5, the European National Funds PON01-02388/1 2007-2013.

Published
2015

16. Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

Author

Vinay, Dass S., Ryan, Elizabeth P., Pawelec, Graham, Talib, Wamidh H., Stagg, John, Elkord, Eyad, Lichtor, Terry, Decker, William K., Whelan, Richard L., Kumara, H.M.C. Shantha, Signori, Emanuela, Honoki, Kanya, Georgakilas, Alexandros G., Amin, Amr, Helferich, William G., Boosani, Chandra S., Guha, Gunjan, Ciriolo, Maria Rosa, Chen, Sophie, and Mohammed, Sulma I.

Subjects
*CANCER treatment, *ANTINEOPLASTIC agents, *DRUG design, *CANCER patients, *CANCER-related mortality, *IMMUNE system
Abstract

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through “equilibrium” and “senescence” before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection. [ABSTRACT FROM AUTHOR]

Published
2015
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