Review
Hematology
Alain Mina, Barbara Pro
Summary: This article summarizes different trials on the treatment of Peripheral T-cell Lymphomas (PTCL), discussing approved targeted agents and novel combination strategies. The article emphasizes the specific biological features of different PTCL subtypes, which should be considered in the design of future clinical trials.
Review
Oncology
Guang Lu, Shikai Jin, Suwen Lin, Yuping Gong, Liwen Zhang, Jingwen Yang, Weiwei Mou, Jun Du
Summary: Peripheral T-cell lymphomas (PTCLs) are aggressive malignancies with poor prognoses. Novel targeted agents, such as histone deacetylase inhibitors (HDACis), are being investigated to improve treatment outcomes. HDACis, including romidepsin, belinostat, and chidamide, have shown efficacy and safety in PTCLs. More HDACis and combination therapies are being studied, and mutation analysis may provide insights into targeted therapies.
CLINICAL EPIGENETICS
(2023)
Article
Chemistry, Medicinal
Yuqi Jiang, Jie Xu, Kairui Yue, Chao Huang, Mengting Qin, Dongyu Chi, Qixin Yu, Yue Zhu, Xiaohan Hou, Tongqiang Xu, Min Li, C. James Chou, Xiaoyang Li
Summary: The study focused on modifying HDAC inhibitors to deactivate the Michael reaction in order to improve their potency. Compound 11h showed significant improvements in both HDAC inhibitory activity and cell-based antitumor assay, demonstrating potential for clinical application and efficacy against AML.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Weiping Liu, Donglu Zhao, Ting Liu, Ting Niu, Yongping Song, Wei Xu, Jie Jin, Qingqing Cai, Huiqiang Huang, Zhiming Li, Ming Hou, Huilai Zhang, Jianfeng Zhou, Jianda Hu, Jianzhen Shen, Yuankai Shi, Yu Yang, Liling Zhang, Weili Zhao, Kaiyang Ding, Lugui Qiu, Huo Tan, Zhihui Zhang, Lihong Liu, Jinghua Wang, Bing Xu, Hui Zhou, Guangxun Gao, Hongwei Xue, Ou Bai, Ru Feng, Xiaobing Huang, Haiyan Yang, Xiaojing Yan, Qingshu Zeng, Peng Liu, Wenyu Li, Min Mao, Hang Su, Xin Wang, Jingyan Xu, Daobin Zhou, Hongyu Zhang, Jun Ma, Zhixiang Shen, Jun Zhu
Summary: A multi-center observational study in China evaluated the efficacy and safety of chidamide treatment for patients with relapsed/refractory PTCL. The study showed that chidamide monotherapy and combination therapies both improved objective response rate and overall survival, with a significant survival advantage compared to international historical records. The most common adverse effects were hematological toxicities, mostly mild to moderate in severity. Further research should investigate the potential benefits of combining chidamide treatment with chemotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Genetics & Heredity
Eliza Mari Kwesi-Maliepaard, Muddassir Malik, Tibor van Welsem, Remco van Doorn, Maarten H. Vermeer, Hanneke Vlaming, Heinz Jacobs, Fred van Leeuwen
Summary: The therapeutic effect of commonly used pan-HDAC inhibitors in CTCL cells may rely on downstream effects that are unrelated to the regulation of DOT1L.
FRONTIERS IN GENETICS
(2022)
Review
Oncology
Peipei Yang, Yali Tao, Ailin Zhao, Kai Shen, He Li, Jinjin Wang, Hui Zhou, Zhongwang Wang, Mengyao Wang, Ying Qu, Li Zhang, Yuhuan Zheng, Ting Niu
Summary: This study systematically evaluated the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and R/R PTCL patients. The results showed that HDAC inhibitors were effective for both untreated and R/R PTCL patients, and the combination of HDAC inhibitor and chemotherapy demonstrated superior efficacy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than other subtypes.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Wei Zhang, Liping Su, Lihong Liu, Yuhuan Gao, Quanshun Wang, Hang Su, Yuhuan Song, Huilai Zhang, Jing Shen, Hongmei Jing, Shuye Wang, Xinan Cen, Hui Liu, Aichun Liu, Zengjun Li, Jianmin Luo, Jianxia He, Jingwen Wang, O. A. O'Connor, Daobin Zhou
Summary: The Chi-CHOEP regimen showed moderate efficacy and good tolerability in previously untreated PTCL patients, with a median PFS of 10.7 months, an overall response rate of 60.2%, and a complete response rate of 40.7%. Adverse events were manageable, predominantly consisting of grade 3/4 neutropenia.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Oncology
Patrick B. Johnston, Amanda F. Cashen, Petros G. Nikolinakos, Anne W. Beaven, Stefan Klaus Barta, Gajanan Bhat, Steven J. Hasal, Sven De Vos, Yasuhiro Oki, Changchun Deng, Francine M. Foss
Summary: This study aimed to determine the maximum tolerated dose of belinostat in combination with CHOP, as well as evaluate its safety, overall response rate, and pharmacokinetics. The results showed that Bel-CHOP combination therapy was well tolerated, with the MTD being the same as single-agent dosing and a high overall response rate.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Meran Keshawa Ediriweera
Summary: Histone acetylation is a crucial epigenetic event and continues to be an area of great interest in biochemical research. The balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs) is disrupted in various human cancers. Histone deacetylase inhibitors (HDACi) have shown promising results in restoring dysregulated histone acetylation profiles and are considered as potential anti-cancer therapeutics. Recent studies have identified odd-chain fatty acids as novel HDACi, further expanding the understanding of fatty acids in cancer therapy.
DRUG DISCOVERY TODAY
(2023)
Article
Virology
Shun Iida, Sohtaro Mine, Keiji Ueda, Tadaki Suzuki, Hideki Hasegawa, Harutaka Katano
Summary: The histone deacetylase inhibitor SBHA was found to efficiently induce KSHV reactivation and apoptosis in PEL cells, suggesting its potential as a tool for KSHV reactivation induction and a novel therapeutic strategy against PEL.
JOURNAL OF VIROLOGY
(2021)
Review
Oncology
Robert Jenke, Nina Ressing, Finn K. Hansen, Achim Aigner, Thomas Buch
Summary: Epigenetic changes can drive cancer malignancy, while histone deacetylase inhibitors (HDACis) hold promise as anticancer drugs due to their ability to target multiple pathways relevant to the disease.
Review
Pharmacology & Pharmacy
Ekta Shirbhate, Ravichandran Veerasamy, Sai H. S. Boddu, Amit K. Tiwari, Harish Rajak
Summary: One significant obstacle in cancer treatment is the decrease in drug efficacy and occurrence of adverse effects. Oncolytic viruses (OVs) have gained interest as a potential method to treat cancer due to their specificity for cancerous tissue and reduced likelihood of adverse effects. Clinical trials have shown that OVs have an acceptable safety profile and are effective in treating certain types of cancer, despite their limited availability. However, further advancements are needed to enhance tumor permeation and improve virus delivery in order to make oncolytic virotherapy more effective.
DRUG DISCOVERY TODAY
(2022)
Review
Oncology
Ping Zhang, Mingzhi Zhang
Summary: CTCLs are a group of heterogeneous diseases involving malignant T cells, with unclear pathogenesis and etiology. Most CTCLs have an indolent course, but once large-cell transformation occurs, it progresses to more aggressive types. Epigenetic drugs have shown certain curative effects and have been selected as third-line drugs for patients with relapsing and refractory CTCL.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Georgiana Toma, Eliza Karapetian, Chiara Massa, Dagmar Quandt, Barbara Seliger
Summary: HDACi treatment increases intracellular protein acetylation level in CD8(+) T cells, but the protein expression profiles are similar between different age groups. CD8(+) T cells from old donors exhibit higher cytokine secretion and activation marker expression compared to those from young donors, which may have clinical relevance.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
John W. R. Schwabe, Andrew G. Jamieson, Lewis J. Archibald, Edward A. Brown, Christopher J. Millard, Peter J. Watson, Naomi S. Robertson, Siyu Wang
Summary: Research suggests that the specific functions of class I HDAC corepressor complexes are partly driven by the recognition of the primary amino acid sequence surrounding a particular lysine position in the histone tail.
ACS CHEMICAL BIOLOGY
(2022)