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Epigenetics immune therapy cancer

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https://www.readbyqxmd.com/read/28536458/epigenetic-priming-restores-the-hla-class-i-antigen-processing-machinery-expression-in-merkel-cell-carcinoma
#1
Cathrin Ritter, Kaiji Fan, Annette Paschen, Sine Reker Hardrup, Soldano Ferrone, Paul Nghiem, Selma Ugurel, David Schrama, J├╝rgen C Becker
Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28511092/epigenetics-and-immunotherapy-the-current-state-of-play
#2
REVIEW
Jennifer Dunn, Sudha Rao
Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant...
May 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28487862/naturally-occurring-canine-invasive-urinary-bladder-cancer-a-complementary-animal-model-to-improve-the-success-rate-in-human-clinical-trials-of-new-cancer-drugs
#3
REVIEW
Christopher M Fulkerson, Deepika Dhawan, Timothy L Ratliff, Noah M Hahn, Deborah W Knapp
Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28486273/zebularine-treatment-induces-mage-a11-expression-and-improves-ctl-cytotoxicity-using-a-novel-identified-hla-a2-restricted-mage-a11-peptide
#4
Jiandong Zhang, Meixiang Sang, Lina Gu, Fei Liu, Weijing Li, Danjing Yin, Yunyan Wu, Shina Liu, Weina Huang, Baoen Shan
Melanoma-associated antigen-A11 (MAGE-A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE-A11 is a potential immunotherapy target in breast cancer. MAGE-A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of MAGE-A11 expression is crucial for the recognition and killing of breast cancer cells by cytotoxic T lymphocytes (CTL). In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested...
May 8, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28447025/metabolic-cooperation-and-competition-in-the-tumor-microenvironment-implications-for-therapy
#5
REVIEW
Seema Gupta, Amrita Roy, Bilikere S Dwarakanath
The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28413671/paraneoplastic-limbic-encephalitis-in-a-patient-with-extensive-disease-small-cell-lung-cancer
#6
Sebastian Ochenduszko, Bartosz Wilk, Joanna Dabrowska, Izabela Herman-Sucharska, Anna Dubis, Miroslawa Puskulluoglu
Paraneoplastic limbic encephalitis (PLE) is a rare disorder infrequently accompanying malignancy, coexisting in ~50% of the cases with small-cell lung cancer (SCLC). The pathomechanism of PLE is considered to be immune-mediated, with production of specific anti-Hu antibodies and activation of T-cells directed against onconeural antigens present on both tumor cells and neurons. We herein report the case of a 50-year-old male patient who, prior to being diagnosed with SCLC, presented with typical symptoms of PLE (seizures, subacute cognitive dysfunction with severe memory impairment, anxiety and hallucinations)...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28410846/initiative-for-molecular-profiling-and-advanced-cancer-therapy-and-challenges-in-the-implementation-of-precision-medicine
#7
Apostolia-Maria Tsimberidou
In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center...
February 10, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28408401/synergistic-immunostimulatory-effects-and-therapeutic-benefit-of-combined-histone-deacetylase-and-bromodomain-inhibition-in-non-small-cell-lung-cancer
#8
Dennis Adeegbe, Yan Liu, Patrick H Lizotte, Yusuke Kamihara, Amir R Aref, Christina Almonte, Ruben Dries, Yuyang Li, Shengwu Liu, Xiaoen Wang, Tiquella Warner-Hatten, Jessica Castrillon, Guo-Cheng Yuan, Neermala Poudel-Neupane, Haikuo Zhang, Jennifer L Guerriero, Shiwei Han, Mark M Awad, David A Barbie, Jerome Ritz, Simon S Jones, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28400597/indicators-of-responsiveness-to-immune-checkpoint-inhibitors
#9
Bradley D Shields, Fade Mahmoud, Erin M Taylor, Stephanie D Byrum, Deepanwita Sengupta, Brian Koss, Giulia Baldini, Seth Ransom, Kyle Cline, Samuel G Mackintosh, Ricky D Edmondson, Sara Shalin, Alan J Tackett
Modulation of the immune system can produce anti-tumor responses in various cancer types, including melanoma. Recently, immune checkpoint inhibitors (ICI), in single agent and combination regimens, have produced durable and long-lasting clinical responses in a subset of metastatic melanoma patients. These monoclonal antibodies, developed against CTLA-4 and PD-1, block immune-inhibitory receptors on activated T-cells, amplifying the immune response. However, even when using anti-CTLA-4 and anti-PD-1 in combination, approximately half of patients exhibit innate resistance and suffer from disease progression...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381242/the-150-most-important-questions-in-cancer-research-and-clinical-oncology-series-questions-15-24-edited-by-chinese-journal-of-cancer
#10
EDITORIAL
(no author information available yet)
To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 10 more questions are presented as follows. Question 15: Can tumor-induced erythrogenesis provide qualified red blood cells for carrying oxygen to distant organs? Question 16: Can we overcome tumor resistance to platinum-containing antineoplastic drugs by activating the sensitivity factors in the tumor? Question 17: How can a cancer cell stay dormant for years? Question 18: Why do cancer cells use distinct transcriptomic and proteomic programs to reach the same metastatic phenotype? Question 19: Why do some cancers regress spontaneously? Question 20: What are the regulatory mechanisms occurring in donor cells that determine selective sorting of biological content into vesicles and their biological consequences in recipient cells? Are the genetic transfer and exchange of biological messages between cells transient? Is the phenotypic manipulation of recipient cells temporary or prolonged and persistent? If extracellular vesicles possess immune-modulatory potential, how could they be exploited for immune interventions and cancer immunotherapy? Presumably the cargo of extracellular vesicles reflects the cells of their origin and can be used for cancer diagnosis, how could the uniform/stringent capture criteria be met universally for applying EVs in point-of-care diagnostics for cancer patients? Question 21: Can we use self-sampling technologies to monitor the tumor genetic alterations for more precise targeted therapy? Can we cure a heterogeneous tumor by sequentially targeting the driver molecules? Question 22: Can we postpone the onset of non-infection-related cancers? Question 23: How many types of cells can jointly form the tumor vasculature to provide blood supply for tumor progression? Question 24: How tumor cells transmit their epigenetic features to daughter cells and maintain the malignant phenotype?...
April 5, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28378010/epigenetic-therapy-for-the-treatment-of-epithelial-ovarian-cancer-a-clinical-review
#11
REVIEW
Haller J Smith, J Michael Straughn, Donald J Buchsbaum, Rebecca C Arend
Despite a good initial response to chemotherapy, the majority of patients with epithelial ovarian cancer will eventually recur and die of their disease. The introduction of targeted therapies to traditional chemotherapy regimens has done little to improve overall survival in women with ovarian cancer. It has become increasingly apparent that the cancer epigenome contributes significantly to the pathogenesis of ovarian cancer and may play an important role in cell proliferation, metastasis, chemoresistance, and immune tolerance...
May 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/28373363/re-engineering-the-pancreas-tumor-microenvironment-a-regenerative-program-hacked
#12
EDITORIAL
Gerard I Evan, Nasun Hah, Trevor D Littlewood, Nicole M Sodir, Tania Campos, Michael Downes, Ronald M Evans
The "hallmarks" of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix, and immune cells. The oncogenically activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immunosuppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue-specific repair mechanism regulated by discrete super enhancer networks...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28373361/pancreatic-cancer-a-riddle-wrapped-in-a-mystery-inside-an-enigma
#13
EDITORIAL
Erkut Borazanci, Chi V Dang, Robert W Robey, Susan E Bates, John A Chabot, Daniel D Von Hoff
Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult-to-treat cancers. With an increasing incidence and inability to make major progress, it represents the very definition of unmet medical need. Progress has been made in understanding the basic biology-systematic genomic sequencing has led to the recognition that PDAC is not typically a heavily mutated tumor, although there are exceptions. The most consistently mutated genes are KRAS, CDKN2A, TP53, and SMAD4/DPC4 Study of familial PDAC has led to the recognition that a variety of defects in DNA repair genes can be associated with the emergence of pancreatic cancer...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28330383/progress-in-nonviral-gene-therapy-for-breast-cancer-and-what-comes-next
#14
Giulia Bottai, Marta Truffi, Fabio Corsi, Libero Santarpia
The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation...
May 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#15
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
May 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28314406/the-role-of-targeted-therapy-in-the-management-of-sinonasal-malignancies
#16
REVIEW
Lawrence Kashat, Christopher H Le, Alexander G Chiu
Cancers develop secondary to genetic and epigenetic changes that provide the cell with a survival advantage that promotes cellular immortality. Malignancy arises when tumors use mechanisms to evade detection and destruction by the immune system. Many malignancies seem to elicit an immune response, yet somehow manage to avoid destruction by the cells of the immune system. Cancers may evade this immune response by numerous mechanisms. Several targeted immune therapies are available that block some of these inhibitory signals and enhance the cell-mediated immune response...
April 2017: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/28278128/cancer-metastasis-tricks-of-the-trade
#17
REVIEW
Rabia Zeeshan, Zeeshan Mutahir
Decades of cancer research have unraveled genetic, epigenetic and molecular pathways leading to plausible therapeutic targets; many of which hold great promise in improving clinical outcomes. Metastatic tumors become evident early on and are one of the major causes of cancer-related fatalities worldwide. This review depicts the sequential events of cancer metastasis. Genetic and epigenetic heterogeneity influences local tumor cell invasion, intravasation, survival in circulation, extravasation and colonization to distant sites...
March 9, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28274154/investigational-drugs-for-the-treatment-of-cervical-cancer
#18
REVIEW
Fabio Barra, Domenica Lorusso, Umberto Leone Roberti Maggiore, Antonino Ditto, Giorgio Bogani, Francesco Raspagliesi, Simone Ferrero
Cervical cancer (CC) is currently the fourth most common malignant disease of women worldwide. Although the incidence and the mortality rates have been decreasing with screening detection and new treatment strategies, a significant number of metastatic or recurrent disease is still diagnosed. For those patients not amenable to curative treatments, such as surgery and radiation, palliative chemotherapy remains the standard of care. As chemotherapy regimens have limited activity, research is focalized on investigating novel pharmacologic strategies...
April 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#19
Kirsty J Flower, Sadaf Ghaem-Maghami, Robert Brown
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#20
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
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