Review
Biochemistry & Molecular Biology
Xue-Song Xiang, Peng-Cheng Li, Wen-Quan Wang, Liang Liu
Summary: Pancreatic cancer is the seventh leading cause of cancer death worldwide and novel treatment options for PDAC are urgently needed. The dysregulation of HDACs has been identified in association with PDAC and may represent a therapeutic breakthrough. However, the contributions of HDACs to PDAC remain controversial and pharmacokinetic challenges limit the application of HDACis in PDAC.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Oncology
Penglin Pan, Gengdu Qin, Bo Wang, Haixin Yu, Jie Chen, Jiaying Liu, Kaijian Bing, Jian Shen, Dianyun Ren, Yuhan Zhao, Wentao Xia, Hui Li, Heshui Wu, Yingke Zhou
Summary: HDAC5 loss is associated with unfavorable prognosis in pancreatic cancer by regulating the expression of cPLA2 and arachidonic acid (AA). Deacetylation of GATA1 by HDAC5 represses cPLA2 expression. Dietary management along with cPLA2-targeted therapy can be an effective strategy for treating HDAC5-deficient pancreatic cancer.
Article
Oncology
Norikazu Masuda, Kenji Tamura, Hiroyuki Yasojima, Akihiko Shimomura, Masataka Sawaki, Min-Jung Lee, Akira Yuno, Jane Trepel, Ryoko Kimura, Yozo Nishimura, Shigehira Saji, Hiroji Iwata
Summary: This study examined the safety, efficacy, and pharmacokinetics of Entinostat monotherapy and combined Entinostat/exemestane in Japanese patients with endocrine therapy-resistant breast cancer. The results showed that both treatments were well tolerated, with some patients achieving stable disease for more than 6 months. Further investigation on the correlation between pharmacokinetics and Ac-K in peripheral blood CD19+ B cells, as well as T-cell activation markers, is warranted.
Article
Cell Biology
Yan Zheng, Le Zhu, Zhao-Yu Qin, Yu Guo, Shun Wang, Min Xue, Ke-Yu Shen, Bei-Yuan Hu, Xu-Feng Wang, Chao-Qun Wang, Lun-Xiu Qin, Qiong-Zhu Dong
Summary: Protein lysine crotonylation is a vital posttranslational modification, especially in histones. This study demonstrates the importance of lysine crotonylation in cytoplastic and mitochondria proteins. It reveals extensive crotonylation in several metabolic enzymes and their involvement in metabolism regulation and pancreatic cancer progression. Additionally, the study highlights the role of crotonylation in the activation of MTHFD1 and its impact on resistance to ferroptosis.
Review
Gastroenterology & Hepatology
Wynne Sim, Wei-Meng Lim, Ling-Wei Hii, Chee-Onn Leong, Chun-Wai Mai
Summary: Immune evasion plays a significant role in the progression and immune resistance of pancreatic cancer, and the role of HDAC in this process is crucial. Despite the lack of significant breakthrough in immunotherapy for pancreatic cancer, targeting HDAC to reverse immune evasion may be a potential strategy.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Review
Pharmacology & Pharmacy
Srimanta Patra, Prakash P. Praharaj, Daniel J. Klionsky, Sujit K. Bhutia
Summary: HDACs inhibit the acetylation of crucial autophagy genes, leading to deregulated autophagy and ACD, facilitating cancer cell survival. Vorinostat interferes with ACD by inhibiting the deacetylation of key autophagic markers, with autophagy-mediated, -associated, or dependent mechanisms depending on the involvement of apoptosis.
DRUG DISCOVERY TODAY
(2022)
Article
Medicine, Research & Experimental
Ting-Yu Chang, Kunal Nepali, Yi-Ying Chen, Yu-Chen S. H. Yang, Kai-Cheng Hsu, Yun Yen, Shiow-Lin Pan, Jing-Ping Liou, Sung-Bau Lee
Summary: The study identifies MPT0L184 as a novel HDAC inhibitor that can induce premature mitosis and potentially combat drug resistance in cancers.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Romana Bohuslavova, Valeria Fabriciova, Laura Lebron-Mora, Jessica Malfatti, Ondrej Smolik, Lukas Valihrach, Sarka Benesova, Daniel Zucha, Zuzana Berkova, Frantisek Saudek, Sylvia M. Evans, Gabriela Pavlinkova
Summary: By using transgenic mouse models, transcriptomic and epigenomic profiling, we found that the absence of Isl1 leads to a diabetic phenotype, loss of alpha cells, disrupted pancreatic islet architecture, downregulation of key ss-cell regulators and maturation markers, and an enrichment in an intermediate endocrine progenitor transcriptomic profile.
CELL AND BIOSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Monika Pieniawska, Katarzyna Izykowska
Summary: Histone deacetylases (HDACs) are enzymes that alter chromatin structure, affecting gene expression. They play important roles in T-cell development and function. This review summarizes the current understanding of the role of HDACs in early T-cell development and mature lymphocyte function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Izabela Szymczak-Pajor, Jozef Drzewoski, Ewa Swiderska, Justyna Strycharz, Anna Gabryanczyk, Jacek Kasznicki, Marta Bogdanska, Agnieszka Sliwinska
Summary: Accumulating evidence suggests that metformin has anticancer properties by inducing apoptosis and inhibiting the growth and proliferation of cancer cells. However, its effect on histone acetylation status remains unclear. Therefore, this study aimed to evaluate the impact of metformin on HATs and HDACs in human pancreatic cancer cell lines.
Review
Oncology
Jayden Sterling, Sharleen V. Menezes, Ramzi H. Abbassi, Lenka Munoz
Summary: Histone lysine demethylases (KDMs) are enzymes that remove methylation marks on lysines in nucleosomes' histone tails, regulating gene transcription and playing important roles in cancer development. KDMs can have activating or repressing effects on gene transcription, regulating the expression of oncogenes and tumor suppressors.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Chemistry, Medicinal
Mengjiao Zhou, Minjian Yuan, Meng Zhang, Chenyi Lei, Omer Aras, Xiaohong Zhang, Feifei An
Summary: Histone deacetylase inhibitors (HDACis) are considered key targets in cancer therapy, but their efficacy as a single therapeutic agent is limited, leading to drug resistance. Combination therapies involving HDACis with other antitumor therapies are being studied to enhance therapeutic efficacy and reduce drug resistance, with a focus on chemotherapy, radiotherapy, phototherapy, targeted therapy, and immunotherapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Chin-King Looi, Li-Lian Gan, Wynne Sim, Ling-Wei Hii, Felicia Fei-Lei Chung, Chee-Onn Leong, Wei-Meng Lim, Chun-Wai Mai
Summary: In this study, the researchers analyzed genomic profiling of PDAC patients and found that high cytotoxic T lymphocytes (CTL) killing activity was correlated with better clinical outcomes. They identified potential small molecules that could restore CTL activity and demonstrated the effectiveness of histone deacetylase inhibitors (HDACi) in reversing CTL resistance in PDAC cells. This research provides insights into new therapeutic strategies for PDAC.
Review
Biochemistry & Molecular Biology
Long Xu, Xiaoyu Yan, Jian Wang, Yuanxin Zhao, Qingqing Liu, Jiaying Fu, Xinyi Shi, Jing Su
Summary: This article provides an overview of ovarian cancer metastasis and the dysregulated expression of HDACs in ovarian cancer. It discusses the roles of HDACs in the regulation of ovarian cancer metastasis and highlights the importance of developing compounds that target HDACs in the future of ovarian cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Jinxiao Ru, Yuxi Wang, Zijia Li, Jiaxing Wang, Changyu Ren, Jifa Zhang
Summary: This manuscript provides a comprehensive overview of the properties and biological functions of HDACs in cancer, discusses the current state of development and limitations of clinical HDAC inhibitors, and analyzes a range of innovative medicinal chemistry techniques that are applied.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)