keyword
https://read.qxmd.com/read/38522008/developments-and-future-prospects-of-personalized-medicine-in-head-and-neck-squamous-cell-carcinoma-diagnoses-and-treatments
#1
REVIEW
Shalindu Malshan Jayawickrama, Piyumi Madhushani Ranaweera, Ratupaskatiye Gedara Gunaratnege Roshan Pradeep, Yovanthi Anurangi Jayasinghe, Kalpani Senevirathna, Abdul Jabbar Hilmi, Rajapakse Mudiyanselage Gamini Rajapakse, Kehinde Kazeem Kanmodi, Ruwan Duminda Jayasinghe
BACKGROUND: Precision healthcare has entered a new era because of the developments in personalized medicine, especially in the diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC). This paper explores the dynamic landscape of personalized medicine as applied to HNSCC, encompassing both current developments and future prospects. RECENT FINDINGS: The integration of personalized medicine strategies into HNSCC diagnosis is driven by the utilization of genetic data and biomarkers...
March 2024: Cancer reports
https://read.qxmd.com/read/38496663/lineage-commitment-pathways-epigenetically-oppose-oncogenic-g%C3%AE-q-11-yap-signaling-in-dormant-disseminated-uveal-melanoma
#2
Rama Kadamb, Melisa Lopez Anton, Timothy J Purwin, Vivian Chua, Lornella Seeneevassen, Jessica Teh, M Angela Nieto, Takami Sato, Mizue Terai, Sergio Roman Roman, Leanne De Koning, Deyou Zheng, Andrew E Aplin, Julio Aguirre-Ghiso
UNLABELLED: The mechanisms driving late relapse in uveal melanoma (UM) patients remains a medical mystery and major challenge. Clinically it is inferred that UM disseminated cancer cells (DCCs) persist asymptomatic for years-to-decades mainly in the liver before they manifest as symptomatic metastasis. Here we reveal using Gαq/11 mut /BAP wt human uveal melanoma models and human UM metastatic samples, that the neural crest lineage commitment nuclear receptor NR2F1 is a key regulator of spontaneous UM DCC dormancy in the liver...
March 8, 2024: bioRxiv
https://read.qxmd.com/read/38473261/targeted-dna-methylation-editing-using-an-all-in-one-system-establishes-paradoxical-activation-of-ebf3
#3
JOURNAL ARTICLE
Rakesh Banerjee, Priyadarshana Ajithkumar, Nicholas Keestra, Jim Smith, Gregory Gimenez, Euan J Rodger, Michael R Eccles, Jisha Antony, Robert J Weeks, Aniruddha Chatterjee
Cutaneous melanoma is rapidly on the rise globally, surpassing the growth rate of other cancers, with metastasis being the primary cause of death in melanoma patients. Consequently, understanding the mechanisms behind this metastatic process and exploring innovative treatments is of paramount importance. Recent research has shown promise in unravelling the role of epigenetic factors in melanoma progression to metastasis. While DNA hypermethylation at gene promoters typically suppresses gene expression, we have contributed to establishing the newly understood mechanism of paradoxical activation of genes via DNA methylation, where high methylation coincides with increased gene activity...
February 23, 2024: Cancers
https://read.qxmd.com/read/38472198/identifying-regulators-of-aberrant-stem-cell-and-differentiation-activity-in-colorectal-cancer-using-a-dual-endogenous-reporter-system
#4
JOURNAL ARTICLE
Sandor Spisak, David Chen, Pornlada Likasitwatanakul, Paul Doan, Zhixin Li, Pratyusha Bala, Laura Vizkeleti, Viktoria Tisza, Pushpamali De Silva, Marios Giannakis, Brian Wolpin, Jun Qi, Nilay S Sethi
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC...
March 12, 2024: Nature Communications
https://read.qxmd.com/read/38468282/gene-editing-technology-to-improve-antitumor-t-cell-functions-in-adoptive-immunotherapy
#5
REVIEW
Yusuke Ito, Satoshi Inoue, Yuki Kagoya
Adoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in hematologic malignancies. However, its efficacy against most of the other tumors is still insufficient, which remains an unmet medical need. Accumulating evidence suggests that modifying specific genes can enhance antitumor T-cell properties...
March 11, 2024: Inflammation and Regeneration
https://read.qxmd.com/read/38453924/crispr-cas9-model-of-prostate-cancer-identifies-kmt2c-deficiency-as-a-metastatic-driver-by-odam-cabs1-gene-cluster-expression
#6
JOURNAL ARTICLE
Huiqiang Cai, Bin Zhang, Johanne Ahrenfeldt, Justin V Joseph, Maria Riedel, Zongliang Gao, Sofie K Thomsen, Ditte S Christensen, Rasmus O Bak, Henrik Hager, Mikkel H Vendelbo, Xin Gao, Nicolai Birkbak, Martin K Thomsen
Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C...
March 7, 2024: Nature Communications
https://read.qxmd.com/read/38401121/prmt1-acts-as-a-suppressor-of-mhc-i-and-anti-tumor-immunity
#7
JOURNAL ARTICLE
Tirta M Djajawi, Lizzy Pijpers, Akash Srivaths, David Chisanga, Kok Fei Chan, Simon J Hogg, Liam Neil, Sarahi Mendoza Rivera, Nenad Bartonicek, Sarah L Ellis, Terry C C Lim Kam Sian, Pouya Faridi, Yang Liao, Bhupinder Pal, Andreas Behren, Wei Shi, Stephin J Vervoort, Ricky W Johnstone, Conor J Kearney
Cancer immunotherapies have demonstrated remarkable success; however, the majority of patients do not respond or develop resistance. Here, we conduct epigenetic gene-targeted CRISPR-Cas9 screens to identify epigenomic factors that limit CD8+ T cell-mediated anti-tumor immunity. We identify that PRMT1 suppresses interferon gamma (Ifnγ)-induced MHC-I expression, thus dampening CD8+ T cell-mediated killing. Indeed, PRMT1 knockout or pharmacological targeting of type I PRMT with the clinical inhibitor GSK3368715 enhances Ifnγ-induced MHC-I expression through elevated STAT1 expression and activation, while re-introduction of PRMT1 in PRMT1-deficient cells reverses this effect...
February 23, 2024: Cell Reports
https://read.qxmd.com/read/38397165/biomarker-ripk3-is-silenced-by-hypermethylation-in-melanoma-and-epigenetic-editing-reestablishes-its-tumor-suppressor-function
#8
JOURNAL ARTICLE
Sarah Arroyo Villora, Paula Castellanos Silva, Tamara Zenz, Ji Sun Kwon, Nico Schlaudraff, Dafina Nitaj, Cornelia Meckbach, Reinhard Dammann, Antje M Richter
For several decades, cancers have demonstrably been one of the most frequent causes of death worldwide. In addition to genetic causes, cancer can also be caused by epigenetic gene modifications. Frequently, tumor suppressor genes are epigenetically inactivated due to hypermethylation of their CpG islands, actively contributing to tumorigenesis. Since CpG islands are usually localized near promoters, hypermethylation of the promoter can have a major impact on gene expression. In this study, the potential tumor suppressor gene Receptor Interacting Serine/Threonine Protein Kinase 3 (RIPK3) was examined for an epigenetic regulation and its gene inactivation in melanomas...
January 28, 2024: Genes
https://read.qxmd.com/read/38394203/therapeutic-targeting-tudor-domains-in-leukemia-via-crispr-scan-assisted-drug-discovery
#9
JOURNAL ARTICLE
Anthony K N Chan, Li Han, Christopher D Delaney, Xueer Wang, Elizaveta Mukhaleva, Mingli Li, Lu Yang, Sheela Pangeni Pokharel, Nicole Mattson, Michelle Garcia, Bintao Wang, Xiaobao Xu, Leisi Zhang, Priyanka Singh, Zeinab Elsayed, Renee Chen, Benjamin Kuang, Jinhui Wang, Yate-Ching Yuan, Bryan Chen, Lai N Chan, Steven T Rosen, David Horne, Markus Müschen, Jianjun Chen, Nagarajan Vaidehi, Scott A Armstrong, Rui Su, Chun-Wei Chen
Epigenetic dysregulation has been reported in multiple cancers including leukemias. Nonetheless, the roles of the epigenetic reader Tudor domains in leukemia progression and therapy remain unexplored. Here, we conducted a Tudor domain-focused CRISPR screen and identified SGF29, a component of SAGA/ATAC acetyltransferase complexes, as a crucial factor for H3K9 acetylation, ribosomal gene expression, and leukemogenesis. To facilitate drug development, we integrated the CRISPR tiling scan with compound docking and molecular dynamics simulation, presenting a generally applicable strategy called CRISPR-Scan Assisted Drug Discovery (CRISPR-SADD)...
February 23, 2024: Science Advances
https://read.qxmd.com/read/38356395/epigenetic-disruption-of-histone-deacetylase-2-accelerated%C3%A2-apoptotic-signaling-and-retarded-malignancy-in-gastric-cells
#10
JOURNAL ARTICLE
Sayedeh Azimeh Hosseini, Mahdi Ghatrehsamani, Hajar Yaghoobi, Fatemeh Elahian, Seyed Abbas Mirzaei
Background: The objective of this research was to determine whether HDAC2 function is associated with gastric cancer progression. Methods: HDAC2 was knocked out in EPG85.257 cells using CRISPR/Cas9 and tumorigenesis pathways were evaluated. Results: Cell proliferation, colony formation, wound healing and transwell invasion were inhibited in ΔHDAC2:EPG85.257 cells. Quantitative analyses revealed a significant downregulation of MMP1, p53, Bax, MAPK1, MAPK3, pro-Caspase3, ERK1/2, p-ERK1/2, AKT1/2/3, p-AKT1/2/3, p-NF-κB (p65), Twist, Snail and p-FAK transcripts/proteins, while SIRT1, PTEN, p21 and Caspase3 were upregulated in ΔHDAC2:EPG85...
February 15, 2024: Epigenomics
https://read.qxmd.com/read/38300873/targeted-demethylation-and-activation-of-nlrc5-augment-cancer-immunogenicity-through-mhc-class-i
#11
JOURNAL ARTICLE
Xin Sun, Toshiyuki Watanabe, Yoshitaka Oda, Weidong Shen, Alaa Ahmad, Ryota Ouda, Paul de Figueiredo, Hidemitsu Kitamura, Shinya Tanaka, Koichi S Kobayashi
Impaired expression of MHC (major histocompatibility complex) class I in cancers constitutes a major mechanism of immune evasion. It has been well documented that the low level of MHC class I is associated with poor prognosis and resistance to checkpoint blockade therapies. However, there is lmited approaches to specifically induce MHC class I to date. Here, we show an approach for robust and specific induction of MHC class I by targeting an MHC class I transactivator (CITA)/NLRC5, using a CRISPR/Cas9-based gene-specific system, designated TRED-I (Targeted reactivation and demethylation for MHC-I)...
February 6, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38298016/applications-of-crispr-epigenome-editors-in-tumor-immunology-and-autoimmunity
#12
REVIEW
Berkay Yahsi, Fahreddin Palaz, Pervin Dincer
Over the past decade, CRISPR-Cas systems have become indispensable tools for genetic engineering and have been used in clinical trials for various diseases. Beyond genome editing, CRISPR-Cas systems can also be used for performing programmable epigenetic modifications. Recent efforts in enhancing CRISPR-based epigenome modifiers have yielded potent tools enabling targeted DNA methylation/demethylation capable of sustaining epigenetic memory through numerous cell divisions. Moreover, it has been understood that during chronic inflammatory states, including cancer, T cells encounter a state called T cell exhaustion that involves elevated inhibitory receptors (e...
January 31, 2024: ACS Synthetic Biology
https://read.qxmd.com/read/38293113/utilizing-a-dual-endogenous-reporter-system-to-identify-functional-regulators-of-aberrant-stem-cell-and-differentiation-activity-in-colorectal-cancer
#13
Sandor Spisak, David Chen, Pornlada Likasitwatanakul, Paul Doan, Zhixin Li, Pratyusha Bala, Laura Vizkeleti, Viktoria Tisza, Pushpamail De Silva, Marios Giannakis, Brian Wolpin, Jun Qi, Nilay S Sethi
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators that regulate these key cellular programs in CRC, we developed an endogenous reporter system by genome-editing human CRC cell lines with knock-in fluorescent reporters at the SOX9 and KRT20 locus to report aberrant stem cell-like activity and differentiation, respectively, and then performed pooled genetic perturbation screens. Constructing a dual reporter system that simultaneously monitored aberrant stem cell-like and differentiation activity in the same CRC cell line improved our signal to noise discrimination...
January 17, 2024: bioRxiv
https://read.qxmd.com/read/38288550/advanced-strategies-for-crispr-cas9-delivery-and-applications-in-gene-editing-therapy-and-cancer-detection-using-nanoparticles-and-nanocarriers
#14
REVIEW
Adric Ru Khiing Hii, Xiaole Qi, Zhenghong Wu
Cancer remains one of the deadliest diseases, and is characterised by the uncontrolled growth of modified human cells. Unlike infectious diseases, cancer does not originate from foreign agents. Though a variety of diagnostic procedures are available; their cost-effectiveness and accessibility create significant hurdles. Non-specific cancer symptoms further complicate early detection, leading to belated recognition of certain cancer. The lack of reliable biomarkers hampers effective treatment, as chemotherapy, radiation therapy, and surgery often result in poor outcomes and high recurrence rates...
January 30, 2024: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://read.qxmd.com/read/38275900/crispring-kras-a-winding-road-with-a-bright-future-in-basic-and-translational-cancer-research
#15
REVIEW
Xian Gong, Jianting Du, Ren-Wang Peng, Chun Chen, Zhang Yang
Once considered "undruggable" due to the strong affinity of RAS proteins for GTP and the structural lack of a hydrophobic "pocket" for drug binding, the development of proprietary therapies for KRAS-mutant tumors has long been a challenging area of research. CRISPR technology, the most successful gene-editing tool to date, is increasingly being utilized in cancer research. Here, we provide a comprehensive review of the application of the CRISPR system in basic and translational research in KRAS-mutant cancer, summarizing recent advances in the mechanistic understanding of KRAS biology and the underlying principles of drug resistance, anti-tumor immunity, epigenetic regulatory networks, and synthetic lethality co-opted by mutant KRAS...
January 22, 2024: Cancers
https://read.qxmd.com/read/38228368/enhancer-mutations-modulate-the-severity-of-chemotherapy-induced-myelosuppression
#16
JOURNAL ARTICLE
Artemy Zhigulev, Zandra Norberg, Julie Cordier, Rapolas Spalinskas, Hassan Bassereh, Niclas Björn, Sailendra Pradhananga, Henrik Gréen, Pelin Sahlén
Non-small cell lung cancer is often diagnosed at advanced stages, and many patients are still treated with classical chemotherapy. The unselective nature of chemotherapy often results in severe myelosuppression. Previous studies showed that protein-coding mutations could not fully explain the predisposition to myelosuppression. Here, we investigate the possible role of enhancer mutations in myelosuppression susceptibility. We produced transcriptome and promoter-interaction maps (using HiCap) of three blood stem-like cell lines treated with carboplatin or gemcitabine...
March 2024: Life Science Alliance
https://read.qxmd.com/read/38165806/metabolic-reprogramming-by-histone-deacetylase-inhibition-preferentially-targets-nrf2-activated-tumors
#17
JOURNAL ARTICLE
Dimitris Karagiannis, Warren Wu, Albert Li, Makiko Hayashi, Xiao Chen, Michaela Yip, Vaibhav Mangipudy, Xinjing Xu, Francisco J Sánchez-Rivera, Yadira M Soto-Feliciano, Jiangbin Ye, Thales Papagiannakopoulos, Chao Lu
The interplay between metabolism and chromatin signaling is implicated in cancer progression. However, whether and how metabolic reprogramming in tumors generates chromatin vulnerabilities remain unclear. Lung adenocarcinoma (LUAD) tumors frequently harbor aberrant activation of the NRF2 antioxidant pathway, which drives aggressive and chemo-resistant disease. Using a chromatin-focused CRISPR screen, we report that NRF2 activation sensitizes LUAD cells to genetic and chemical inhibition of class I histone deacetylases (HDACs)...
December 30, 2023: Cell Reports
https://read.qxmd.com/read/38093832/applications-of-innovation-technologies-for-personalized-cancer-medicine-stem-cells-and-gene-editing-tools
#18
REVIEW
Akbar Hasanzadeh, Arefeh Ebadati, Lida Dastanpour, Amir R Aref, Parham Sahandi Zangabad, Alireza Kalbasi, Xiaofeng Dai, Geeta Mehta, Amir Ghasemi, Yousef Fatahi, Suhasini Joshi, Michael R Hamblin, Mahdi Karimi
Personalized medicine is a new approach toward safer and even cheaper treatments with minimal side effects and toxicity. Planning a therapy based on individual properties causes an effective result in a patient's treatment, especially in a complex disease such as cancer. The benefits of personalized medicine include not only early diagnosis with high accuracy but also a more appropriate and effective therapeutic approach based on the unique clinical, genetic, and epigenetic features and biomarker profiles of a specific patient's disease...
December 8, 2023: ACS Pharmacology & Translational Science
https://read.qxmd.com/read/38093346/dynamic-altruistic-cooperation-within-breast-tumors
#19
JOURNAL ARTICLE
Muhammad Sufyan Bin Masroni, Kee Wah Lee, Victor Kwan Min Lee, Siok Bian Ng, Chao Teng Law, Kok Siong Poon, Bernett Teck-Kwong Lee, Zhehao Liu, Yuen Peng Tan, Wee Ling Chng, Steven Tucker, Lynette Su-Mien Ngo, George Wai Cheong Yip, Min En Nga, Susan Swee Shan Hue, Thomas Choudary Putti, Boon Huat Bay, Qingsong Lin, Lihan Zhou, Mikael Hartman, Tze Ping Loh, Manikandan Lakshmanan, Sook Yee Lee, Vinay Tergaonkar, Huiwen Chua, Adeline Voon Hui Lee, Eric Yew Meng Yeo, Mo-Huang Li, Chan Fong Chang, Zizheng Kee, Karen Mei-Ling Tan, Soo Yong Tan, Evelyn Siew-Chuan Koay, Marco Archetti, Sai Mun Leong
BACKGROUND: Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism's survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance. METHODS: MicroRNA profiling was performed on circulating tumor cells collected from the blood of treated breast cancer patients...
December 14, 2023: Molecular Cancer
https://read.qxmd.com/read/38065340/galectin-7-induction-by-ehmt2-inhibition-enhances-immunity-in-mss-colorectal-cancer
#20
JOURNAL ARTICLE
Lei Sun, Ruonian Liu, Zong-Jian Wu, Zheng-Yu Liu, Arabella H Wan, Shijia Yan, Chuwei Liu, Heng Liang, Min Xiao, Nan You, Yawen Lou, Yuan Deng, Xianzhang Bu, Dongshi Chen, Jun Huang, Xiaolei Zhang, Dong-Ming Kuang, Guohui Wan
BACKGROUND & AIMS: Despite immunotherapy shows substantial advancement in colorectal cancer (CRC) with microsatellite instability high (MSI), it has limited efficacy for CRC with microsatellite stability (MSS). Identifying combinations that reverse immune suppression and prime MSS tumors for current immunotherapy approaches remains an urgent need. METHODS: An in vitro CRISPR screen was performed using co-culture models of primary tumor cells and autologous immune cells from MSS CRC patients to identify epigenetic targets that could enhance immunotherapy efficacy in MSS tumors...
December 6, 2023: Gastroenterology
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