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Epigenetics immune therapy cancer

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https://www.readbyqxmd.com/read/29311580/lsd1-activation-promotes-inducible-emt-programs-and-modulates-the-tumour-microenvironment-in-breast-cancer
#1
T Boulding, R D McCuaig, A Tan, K Hardy, F Wu, J Dunn, M Kalimutho, C R Sutton, J K Forwood, A G Bert, G J Goodall, L Malik, D Yip, J E Dahlstrom, A Zafar, K K Khanna, S Rao
Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29305654/spontaneous-regression-of-neuroblastoma
#2
REVIEW
Garrett M Brodeur
Neuroblastomas are characterized by heterogeneous clinical behavior, from spontaneous regression or differentiation into a benign ganglioneuroma, to relentless progression despite aggressive, multimodality therapy. Indeed, neuroblastoma is unique among human cancers in terms of its propensity to undergo spontaneous regression. The strongest evidence for this comes from the mass screening studies conducted in Japan, North America and Europe and it is most evident in infants with stage 4S disease. This propensity is associated with a pattern of genomic change characterized by whole chromosome gains rather than segmental chromosome changes but the mechanism(s) underlying spontaneous regression are currently a matter of speculation...
January 5, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29299180/regulation-of-pd-1-pd-l1-pathway-and-resistance-to-pd-1-pd-l1-blockade
#3
REVIEW
Jie Bai, Zhitao Gao, Xiang Li, Liang Dong, Weidong Han, Jing Nie
Immune checkpoint blockades, such as inhibitors against programmed death 1 (PD-1) and its ligand (PD-L1), have received extensive attention in the past decade because of their dramatic clinical outcomes in advanced malignancies. However, both primary and acquired resistance becomes one of the major obstacles, which greatly limits the long-lasting effects and wide application of PD-1/PD-L1 blockade therapy. PD-1/PD-L1 both regulates and is regulated by cellular signaling pathways and epigenetic modification, thus inhibiting the proliferation and effector function of T and B cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#4
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29209524/heterogeneity-of-colon-cancer-from-bench-to-bedside
#5
REVIEW
Marco C Merlano, Cristina Granetto, Elena Fea, Vincenzo Ricci, Ornella Garrone
The large bowel shows biomolecular, anatomical and bacterial changes that proceed from the proximal to the distal tract. These changes account for the different behaviour of colon cancers arising from the diverse sides of the colon-rectum as well as for the sensitivity to the therapy, including immunotherapy. The gut microbiota plays an important role in the modulation of the immune response and differs between the right colon cancer and the left colorectal cancer. The qualitative and quantitative difference of the commensal bacteria between the right side and the left side induces epigenetic changes in the intestinal epithelial cells as well as in the resident immune population...
2017: ESMO Open
https://www.readbyqxmd.com/read/29203668/epigenetic-therapy-activates-type-i-interferon-signaling-in-murine-ovarian-cancer-to-reduce-immunosuppression-and-tumor-burden
#6
Meredith L Stone, Katherine B Chiappinelli, Huili Li, Lauren M Murphy, Meghan E Travers, Michael J Topper, Dimitrios Mathios, Michael Lim, Ie-Ming Shih, Tian-Li Wang, Chien-Fu Hung, Vipul Bhargava, Karla R Wiehagen, Glenn S Cowley, Kurtis E Bachman, Reiner Strick, Pamela L Strissel, Stephen B Baylin, Cynthia A Zahnow
Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29202431/triple-negative-breast-cancer-emerging-therapeutic-modalities-and-novel-combination-therapies
#7
REVIEW
Alice Lee, Mustafa B A Djamgoz
Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer which lacks oestrogen receptors, progesterone receptors and HER2 amplification, thereby making it difficult to target therapeutically. In addition, TNBC has the highest rates of metastatic disease and the poorest overall survival of all breast cancer subtypes. Resultantly, development of targeted therapies for TNBC is urgently needed. Recent efforts aimed at molecular characterisation of TNBCs have revealed various emerging therapeutic targets including PARP1, receptor and non-receptor tyrosine kinases, immune-checkpoints, androgen receptor and epigenetic proteins...
January 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29195073/epigenetic-therapy-ties-myc-depletion-to-reversing-immune-evasion-and-treating-lung-cancer
#8
Michael J Topper, Michelle Vaz, Katherine B Chiappinelli, Christina E DeStefano Shields, Noushin Niknafs, Ray-Whay Chiu Yen, Alyssa Wenzel, Jessica Hicks, Matthew Ballew, Meredith Stone, Phuoc T Tran, Cynthia A Zahnow, Matthew D Hellmann, Valsamo Anagnostou, Pamela L Strissel, Reiner Strick, Victor E Velculescu, Stephen B Baylin
Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29184195/chromatin-dependencies-in-cancer-and-inflammation
#9
REVIEW
Ivan Marazzi, Benjamin D Greenbaum, Diana H P Low, Ernesto Guccione
Multiple cell-signalling pathways converge on chromatin to induce gene expression programmes. The inducible transcriptional programmes that are established as a result of inflammatory or oncogenic signals are controlled by shared chromatin regulators. Therapeutic targeting of such chromatin dependencies has proved effective for controlling tumorigenesis and for preventing immunopathologies that are driven by overt inflammation. In this Review, we discuss how chromatin dependencies are established to regulate the expression of key oncogenes and inflammation-promoting genes and how a better mechanistic understanding of such chromatin dependencies can be leveraged to improve the magnitude, timing, duration and selectivity of cell responses with the aim of minimizing unwanted cellular and systemic effects...
November 29, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#10
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29100458/dna-methylation-hydroxymethylation-in-melanoma
#11
REVIEW
Siqi Fu, Haijing Wu, Huiming Zhang, Christine G Lian, Qianjin Lu
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29054858/mirna-directed-cancer-therapies-implications-in-melanoma-intervention
#12
Anita Thyagarajan, Ahmed Shaban, Ravi P Sahu
Acquired tumor resistance to cancer therapies pose major challenges in the treatment of cancers including melanoma. Among several signaling pathways or factors that affect neocarcinogenesis, cancer progression and therapies, altered microRNAs (miRNAs) expression has been identified as crucial players in modulating the key pathways governing these events. While studies on miRNA field has grown exponentially in the last decade, much remains to be discovered, particularly with respect to their roles in cancer therapies...
October 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#13
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29018149/hypothesis-stimulation-of-trained-immunity-as-adjunctive-immunotherapy-in-cancer
#14
REVIEW
Mihai G Netea, Leo A B Joosten, Jos W M van der Meer
Cancer immunotherapy has steadily progressed during the past decades, with checkpoint inhibitor therapy becoming the latest and one of the most promising treatments. Despite the progress, most of the patients do not respond or develop resistance, and novel additional approaches are needed to improve the clinical effectiveness of immunotherapy. Trained immunity (TI) has been described recently as a process of epigenetic and metabolic reprogramming that induces a long-term enhanced function of innate immune cells...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28948003/the-hedgehog-gli-pathway-in-embryonic-development-and-cancer-implications-for-pulmonary-oncology-therapy
#15
REVIEW
Leonel Armas-López, Joaquín Zúñiga, Oscar Arrieta, Federico Ávila-Moreno
Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28939082/epigenetic-therapy-regulates-the-expression-of-aldh1-and-immunologic-response-relevance-to-the-prognosis-of-oral-cancer
#16
Ming-Shao Tsai, Wen-Cheng Chen, Chia-Hsuan Lai, Yu-Yen Chen, Miao-Fen Chen
OBJECTIVES: Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and shown to identify cancer stem cells (CSC)-like cells. We aimed to investigate the significance of ALDH1 in oral squamous cell carcinoma (OSCC) and its correlation with DNMT3b and immune evasion in the present study. METHODS: We retrospectively analyzed the clinical outcomes of OSCC patients and examined its correlation with the levels of ALDH1 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in the peripheral blood...
October 2017: Oral Oncology
https://www.readbyqxmd.com/read/28932075/role-of-tissue-microenvironment-resident-adipocytes-in-colon-cancer
#17
EDITORIAL
Maria Tabuso, Shervanthi Homer-Vanniasinkam, Raghu Adya, Ramesh P Arasaradnam
Colorectal cancer (CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment (TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors (angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28931558/pathological-processes-and-therapeutic-advances-in-radioiodide-refractory-thyroid-cancer
#18
Marika H Tesselaar, Jan Wa Smit, James Nagarajah, Romana T Netea-Maier, Theo S Plantinga
Whereas in most patients with non-medullary thyroid cancer (TC) disease remission is achieved by thyroidectomy and ablation of tumor remnants by radioactive iodide (RAI), a substantial subgroup of patients with metastatic disease present tumor lesions that have acquired RAI resistance as a result of dedifferentiation. Although oncogenic mutations in BRAF, TERT promoter and TP53 are associated with an increased propensity for induction of dedifferentiation, the role of genetic and epigenetic aberrations and their effects on important intracellular signaling pathways is not yet fully elucidated...
September 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28930219/qigong-in-cancer-care-theory-evidence-base-and-practice
#19
Penelope Klein
Background: The purpose of this discussion is to explore the theory, evidence base, and practice of Qigong for individuals with cancer. Questions addressed are: What is qigong? How does it work? What evidence exists supporting its practice in integrative oncology? What barriers to wide-spread programming access exist? Methods: Sources for this discussion include a review of scholarly texts, the Internet, PubMed, field observations, and expert opinion. Results: Qigong is a gentle, mind/body exercise integral within Chinese medicine...
January 12, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28928129/new-advances-and-challenges-of-targeting-cancer-stem-cells
#20
Nurmaa K Dashzeveg, Rokana Taftaf, Erika K Ramos, Luke Torre-Healy, Anastasia Chumakova, Daniel J Silver, Tyler J Alban, Maksim Sinyuk, Praveena S Thiagarajan, Awad M Jarrar, Soumya M Turaga, Caner Saygin, Erin Mulkearns-Hubert, Masahiro Hitomi, Jeremy N Rich, Stanton L Gerson, Justin D Lathia, Huiping Liu
The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20-23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop...
October 1, 2017: Cancer Research
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