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Epigenetics immune therapy cancer

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https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#1
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
#2
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
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#3
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#4
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#5
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28011470/advances-in-experimental-targeted-therapy-and-immunotherapy-for-patients-with-glioblastoma-multiforme
#6
REVIEW
Jiri Polivka, Jiri Polivka, Lubos Holubec, Tereza Kubikova, Vladimir Priban, Ondrej Hes, Kristyna Pivovarcikova, Inka Treskova
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28000527/epigenetic-regulation-of-immune-checkpoints-another-target-for-cancer-immunotherapy
#7
Mahmoud A Ali, Marwa Matboli, Marwa Tarek, Maged Reda, Kamal M Kamal, Mahmoud Nouh, Ahmed M Ashry, Ahmed Fath El-Bab, Hend A Mesalam, Ayman El-Sayed Shafei, Omar Abdel-Rahman
Epigenetic changes in oncogenes and tumor-suppressor genes contribute to carcinogenesis. Understanding the epigenetic and genetic components of tumor immune evasion is crucial. Few cancer genetic mutations have been linked to direct correlations with immune evasion. Studies on the epigenetic modulation of the immune checkpoints have revealed a critical interaction between epigenetic and immune modulation. Epigenetic modifiers can activate many silenced genes. Some of them are immune checkpoints regulators that turn on immune responses and others turn them off resulting in immune evasion...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27999738/the-interplay-of-epigenetic-therapy-and-immunity-in-locally-recurrent-or-metastatic-estrogen-receptor-positive-breast-cancer-correlative-analysis-of-encore-301-a-randomized-placebo-controlled-phase-ii-trial-of-exemestane-with-or-without-entinostat
#8
Yusuke Tomita, Min-Jung Lee, Sunmin Lee, Saori Tomita, Saranya Chumsri, Scott Cruickshank, Peter Ordentlich, Jane B Trepel
Entinostat, a class I-selective histone deacetylase inhibitor, has shown promising activity in ENCORE 301, a randomized, placebo-controlled, phase II trial of exemestane with or without entinostat in women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on a nonsteroidal aromatase inhibitor. ENCORE 301 showed an 8.3-mo improvement in median overall survival among patients who received entinostat. We investigated the impact of entinostat on immune subsets with CD40, HLA-DR, and immune checkpoint receptor expression analyses in 34 patient blood samples from ENCORE 301...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27982549/latest-insights-into-pathogenesis-of-mycosis-fungoides-and-cutaneous-t-cell-lymphoma
#9
Laura Y McGirt
Cutaneous T-cell lymphoma (CTCL) is a rare but increasing malignancy whose protean manifestations necessarily present in the integument, but can also spread to involve blood, lymph nodes and internal organs. We have developed efficacious and varied therapies to treat early and advanced stage disease, but there are still many who suffer tremendously from this illness. Although the pathogenesis of this cancer remains frustratingly elusive, over the last 200 years we have generated a robust body of evidence that points toward possible singular as well as multifactorial etiologies...
April 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/27932423/integrated-genomic-analysis-of-survival-outliers-in-glioblastoma
#10
Sen Peng, Harshil Dhurv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E Sloan, Quinn T Ostrom, Jill S Barnholtz-Sloan, Nhan L Tran, Michael E Berens
BACKGROUND: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). METHODS: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27923508/surfacing-role-of-probiotics-in-cancer-prophylaxis-and-therapy-a-systematic-review
#11
REVIEW
Subramanyam Dasari, Chandrasekhar Kathera, Avilala Janardhan, Arthala Praveen Kumar, Buddolla Viswanath
Cancers figure among the most important causes of morbidity and mortality worldwide. Cancer and its associated infections are always complicated even when specific cancer regimens are available. It is well proved that Lactobacillus and other probiotic bacteria can modulate-ameliorate specific mechanisms against various infections including cancers. The present systematic review is intended to focus on the 'cellular and molecular mechanisms' of probiotic bacteria in the prevention and treatment of various cancers...
November 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#12
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27902459/anti-tumor-activity-of-metformin-from-metabolic-and-epigenetic-perspectives
#13
REVIEW
Xilan Yu, Wuxiang Mao, Yansheng Zhai, Chong Tong, Min Liu, Lixin Ma, Xiaolan Yu, Shanshan Li
Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887656/looking-beyond-the-cancer-cell-for-effective-drug-combinations
#14
Jonathan R Dry, Mi Yang, Julio Saez-Rodriguez
Combinations of therapies are being actively pursued to expand therapeutic options and deal with cancer's pervasive resistance to treatment. Research efforts to discover effective combination treatments have focused on drugs targeting intracellular processes of the cancer cells and in particular on small molecules that target aberrant kinases. Accordingly, most of the computational methods used to study, predict, and develop drug combinations concentrate on these modes of action and signaling processes within the cancer cell...
November 25, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27865897/enigmas-in-tumor-resistance-to-kinase-inhibitors-and-calculation-of-the-drug-resistance-index-for-cancer-dric
#15
REVIEW
C I Edvard Smith
Darwinian selection is also applicable when antibiotics, the immune system or other host factors shape the repertoire of microorganisms, and similarly, clonal selection is the hallmark of tumor evolution. The ongoing revolution in new anti-cancer treatment modalities, combined with an unprecedented precision in characterizing malignant clones at the level below one percent, profoundly improves the understanding of repertoire-tuning mechanisms. There is no fundamental difference between selection of the tumor cells in the presence, or absence, of therapy...
November 16, 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27854240/the-impact-of-chemotherapy-radiation-and-epigenetic-modifiers-in-cancer-cell-expression-of-immune-inhibitory-and-stimulatory-molecules-and-anti-tumor-efficacy
#16
REVIEW
Jessica Ann Chacon, Keith Schutsky, Daniel J Powell
Genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers are used for the treatment of cancer due to their apoptotic effects on the aberrant cells. However, these therapies may also induce widespread changes within the immune system and cancer cells, which may enable tumors to avoid immune surveillance and escape from host anti-tumor immunity. Genomic destabilizers can induce immunogenic death of tumor cells, but also induce upregulation of immune inhibitory ligands on drug-resistant cells, resulting in tumor progression...
November 14, 2016: Vaccines
https://www.readbyqxmd.com/read/27811314/epigenetic-treatment-of-pancreatic-cancer-is-there-a-therapeutic-perspective-on-the-horizon
#17
REVIEW
Elisabeth Hessmann, Steven A Johnsen, Jens T Siveke, Volker Ellenrieder
Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most aggressive malignancies with a 5-year survival rate of <7%. Due to growing incidence, late diagnosis and insufficient treatment options, PDAC is predicted to soon become one of the leading causes of cancer-related death. Although intensified cytostatic combinations, particularly gemcitabine plus nab-paclitaxel and the folinic acid, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX) protocol, provide some improvement in efficacy and survival compared with gemcitabine alone, a breakthrough in the treatment of metastatic pancreatic cancer remains out of sight...
January 2017: Gut
https://www.readbyqxmd.com/read/27796306/structural-basis-of-checkpoint-blockade-by-monoclonal-antibodies-in-cancer-immunotherapy
#18
Ju Yeon Lee, Hyun Tae Lee, Woori Shin, Jongseok Chae, Jaemo Choi, Sung Hyun Kim, Heejin Lim, Tae Won Heo, Kyeong Young Park, Yeon Ji Lee, Seong Eon Ryu, Ji Young Son, Jee Un Lee, Yong-Seok Heo
Cancer cells express tumour-specific antigens derived via genetic and epigenetic alterations, which may be targeted by T-cell-mediated immune responses. However, cancer cells can avoid immune surveillance by suppressing immunity through activation of specific inhibitory signalling pathways, referred to as immune checkpoints. In recent years, the blockade of checkpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies has enabled the development of breakthrough therapies in oncology, and four therapeutic antibodies targeting these checkpoint molecules have been approved by the FDA for the treatment of several types of cancer...
October 31, 2016: Nature Communications
https://www.readbyqxmd.com/read/27792246/inhibition-of-histone-deacetylases-in-melanoma-a-perspective-from-bench-to-bedside
#19
REVIEW
Eva Hornig, Markus V Heppt, Saskia A Graf, Thomas Ruzicka, Carola Berking
Histone deacetylases (HDACs) are critically involved in epigenetic gene regulation through alterations of the chromatin status of DNA. Aberrant expression, dysregulation of their enzymatic activity or imbalances between HDACs and histone acetyltransferases are likely involved in the development and progression of cancer. Pharmacologic inhibition of HDACs shows potent antitumor activity in a panel of malignancies such as colon or gastric cancer and multiple myeloma. In this review, we summarize the current knowledge of HDACs in melanoma and evaluate the application of HDAC inhibition from an experimental and clinical perspective...
November 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27770445/understanding-the-epigenetic-regulation-of-tumours-and-their-microenvironments-opportunities-and-problems-for-epigenetic-therapy
#20
REVIEW
Man Liu, Jingying Zhou, Zhiwei Chen, Alfred Sze-Lok Cheng
The tumour microenvironment plays an instrumental role in cancer development, progression and treatment response/resistance. Accumulating evidence is underscoring the fundamental importance of epigenetic regulation in tumour immune evasion. Following many pioneering discoveries demonstrating malignant transformation through epigenetic anomalies ('epimutations'), there is also a growing emphasis on elucidating aberrant epigenetic mechanisms that reprogramme the milieu of tumour-associated immune and stromal cells towards an immunosuppressive state...
January 2017: Journal of Pathology
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