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5 results on '"Yang, Xujuan"'

1. Therapeutic targeting of replicative immortality

Author

Yaswen, Paul, MacKenzie, Karen L, Keith, W Nicol, Hentosh, Patricia, Rodier, Francis, Zhu, Jiyue, Firestone, Gary L, Matheu, Ander, Carnero, Amancio, Bilsland, Alan, Sundin, Tabetha, Honoki, Kanya, Fujii, Hiromasa, Georgakilas, Alexandros G, Amedei, Amedeo, Amin, Amr, Helferich, Bill, Boosani, Chandra S, Guha, Gunjan, Ciriolo, Maria Rosa, Chen, Sophie, Mohammed, Sulma I, Azmi, Asfar S, Bhakta, Dipita, Halicka, Dorota, Niccolai, Elena, Aquilano, Katia, Ashraf, S Salman, Nowsheen, Somaira, and Yang, Xujuan

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Genetics, Cancer, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Antineoplastic Agents, Cell Proliferation, Cell Transformation, Neoplastic, Cellular Senescence, Genomic Instability, Humans, Molecular Targeted Therapy, Neoplasms, Phosphatidylinositol 3-Kinases, Signal Transduction, Telomerase, Tumor Suppressor Protein p53, Senescence, Oncogenic stress, p53, pRB, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy.

Published
2015

2. Investigating the optimal size of anticancer nanomedicine

Author

Tang, Li, Yang, Xujuan, Yin, Qian, Cai, Kaimin, Wang, Hua, Chaudhury, Isthier, Yao, Catherine, Zhou, Qin, Kwon, Mincheol, Hartman, James A., Dobrucki, Iwona T., Dobrucki, Lawrence W., Borst, Luke B., Lezmi, Stéphane, Helferich, William G., Ferguson, Andrew L., Fan, Timothy M., and Cheng, Jianjun

Published
2014

3. Broad targeting of angiogenesis for cancer prevention and therapy

Author

Wang, Zongwei, Dabrosin, Charlotta, Yin, Xin, Fuster, Mark M., Arreola, Alexandra, Rathmell, W. Kimryn, Generali, Daniele, Nagaraju, Ganji P., El-Rayes, Bassel, Ribatti, Domenico, Chen, Yi Charlie, Honoki, Kanya, Fujii, Hiromasa, Georgakilas, Alexandros G., Nowsheen, Somaira, Amedei, Amedeo, Niccolai, Elena, Amin, Amr, Ashraf, S. Salman, Helferich, Bill, Yang, Xujuan, Guha, Gunjan, Bhakta, Dipita, Ciriolo, Maria Rosa, Aquilano, Katia, Chen, Sophie, Halicka, Dorota, Mohammed, Sulma I., Azmi, Asfar S., Bilsland, Alan, Keith, W. Nicol, Jensen, Lasse D., Wang, Zongwei, Dabrosin, Charlotta, Yin, Xin, Fuster, Mark M., Arreola, Alexandra, Rathmell, W. Kimryn, Generali, Daniele, Nagaraju, Ganji P., El Rayes, Bassel, Ribatti, Domenico, Chen, Yi Charlie, Honoki, Kanya, Fujii, Hiromasa, Georgakilas, Alexandros G., Nowsheen, Somaira, Amedei, Amedeo, Niccolai, Elena, Amin, Amr, Ashraf, S. Salman, Helferich, Bill, Yang, Xujuan, Guha, Gunjan, Bhakta, Dipita, Ciriolo, Maria Rosa, Aquilano, Katia, Chen, Sophie, Halicka, Dorota, Mohammed, Sulma I., Azmi, Asfar S., Bilsland, Alan, Keith, W. Nicol, and Jensen, Lasse D.

Subjects
Cancer och onkologi, Cancer Research, Neovascularization, Pathologic, Anti-angiogenic, Phytochemicals, Angiogenesis Inhibitors, Review, Phytochemical, Antineoplastic Agents, Phytogenic, Angiogenesis Cancer Phytochemicals Treatment Anti-angiogenic, Treatment, Angiogenesi, Angiogenesis, Cancer, Cancer and Oncology, Neoplasms, Blood Vessels, Humans, Immunotherapy, Settore BIO/10, Cell Proliferation
Abstract

Deregulation of angiogenesis - the growth of new blood vessels from an existing vasculature - is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies. Funding agencies: Swedish Society for Medical Research; Goesta Fraenkel Foundation; Ake Wibergs Foundation; Ollie och Elof Ericssons Foundation; Karolinska Institute; Linkoping University; University of Glasgow; Beatson Oncology Center Fund; Cancer Research UK grant

Published
2015
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4. 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

5. Broad targeting of resistance to apoptosis in cancer

Author

Nagi B. Kumar, Chandra S. Boosani, Amr Amin, Gunjan Guha, Helen M. Coley, Ramzi M. Mohammad, Gian Luigi Russo, S. Salman Ashraf, Kanya Honoki, Carmela Fimognari, Swapan K. Ray, William G. Helferich, Maria Rosa Ciriolo, Markus D. Siegelin, Abbas Samadi, Hiromasa Fujii, Irfana Muqbil, Asfar S. Azmi, Huanjie Yang, Hsue-Yin Hsu, W. Nicol Keith, Elena Niccolai, Leroy Lowe, Amedeo Amedei, Dorota Halicka, Sulma I. Mohammed, Liang Tzung Lin, Q. Ping Dou, Clement G. Yedjou, Alexandros G. Georgakilas, Mrinmay Chakrabarti, Somaira Nowsheen, Sophie Chen, Xujuan Yang, James D. Morre, Dipita Bhakta, Alan Bilsland, Katia Aquilano, Carmela Spagnuolo, Mohammad, Ramzi M., Muqbil, Irfana, Lowe, Leroy, Yedjou, Clement, Hsu, Hsue-Yin, Lin, Liang-Tzung, Siegelin, Markus David, Fimognari, Carmela, Kumar, Nagi B., Dou, Q. Ping, Yang, Huanjie, Samadi, Abbas K., Russo, Gian Luigi, Spagnuolo, Carmela, Ray, Swapan K., Chakrabarti, Mrinmay, Morre, James D., Coley, Helen M., Honoki, Kanya, Fujii, Hiromasa, Georgakilas, Alexandros G., Amedei, Amedeo, Niccolai, Elena, Amin, Amr, Ashraf, S. Salman, Helferich, William G., Yang, Xujuan, Boosani, Chandra S., Guha, Gunjan, Bhakta, Dipita, Ciriolo, Maria Rosa, Aquilano, Katia, Chen, Sophie, Mohammed, Sulma I., Keith, W. Nicol, Bilsland, Alan, Halicka, Dorota, Nowsheen, Somaira, and Azmi, Asfar S.

Subjects
Programmed cell death, Cancer Research, Necroptosis, Antineoplastic Agents, Apoptosis, Biology, Nuclear transporters, Article, chemopreventive agents, Necrosis, Heat shock protein, Neoplasms, medicine, Autophagy, Humans, Nuclear transporters, natural chemopreventive agents, Molecular Targeted Therapy, Apoptosis evasion, Settore BIO/10, Nuclear transporters, natural chemopreventive agent, Cell Proliferation, natural, Cancer, Apoptosi, medicine.disease, Necrosi, 3. Good health, Cell biology, Drug Resistance, Neoplasm, Cancer cell, Signal transduction, natural chemopreventive agents, Signal Transduction
Abstract

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.

Published
2015

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