Review
Pharmacology & Pharmacy
Zhixiong Zhang, Guan Wang, Yuyan Li, Dongsheng Lei, Jin Xiang, Liang Ouyang, Yanyan Wang, Jinliang Yang
Summary: DNA methylation is an important epigenetic process that regulates gene expression and has become a promising target for cancer treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Felipe Pantoja Mesquita, Pedro Filho Noronha Souza, Emerson Lucena da Silva, Luina Benevides Lima, Lais Lacerda Brasil de Oliveira, Caroline Aquino Moreira-Nunes, William J. Zuercher, Rommel Mario Rodriguez Burbano, Maria Elisabete Amaral de Moraes, Raquel Carvalho Montenegro
Summary: This study identified a novel kinase target in gastric cancer cells as a potential therapeutic strategy. The inhibition of this kinase target showed promising results in reducing cell migration and increasing cell survival, and it may serve as a biomarker for prognosis and therapeutic management.
Review
Chemistry, Multidisciplinary
Yoshihiro Sohtome, Tadahiro Shimazu, Yoichi Shinkai, Mikiko Sodeoka
Summary: Developing synthetic strategies to construct covalent bonds is a common research topic among synthetic chemists. The success of such strategies relies on the tunability of conditions such as catalysts, reagents, solvents, and reaction temperature. However, controlling chemical reactions in living cells poses challenges due to a smaller number of hit substrates and a complex and inflexible environment. The use of chemical methylome analysis serves as an example of bridging the gap between chemistry and biology in this context.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Engineering, Environmental
Xiaoding Cheng, Chong Zhang, Kun Shen, Huifan Liu, Caihong Bai, Qihang Ding, Mengting Guan, Junzhu Wu, Zhiquan Tian, Deliang Chen, Lin Cai, Xuechuan Hong, Yuling Xiao
Summary: This study evaluates a unique strategy using a NIR-II fluorescent photosensitizer in combination with a DDR inhibitor to improve the therapeutic efficacy of osteosarcoma treatment. The results demonstrate that this strategy significantly enhances anti-tumor effects and has good bioavailability with low toxicity.
CHEMICAL ENGINEERING JOURNAL
(2022)
Review
Genetics & Heredity
Elena Alexandrova, Annamaria Salvati, Giovanni Pecoraro, Jessica Lamberti, Viola Melone, Assunta Sellitto, Francesca Rizzo, Giorgio Giurato, Roberta Tarallo, Giovanni Nassa, Alessandro Weisz
Summary: The histone lysine methyltransferase DOT1L plays a crucial role in the epigenetic regulation of gene expression and is associated with embryonic development, adult tissues functions, and leukemogenesis. Abnormal expression and activity of DOT1L are linked to poor survival and increased aggressiveness of several solid tumors. This review summarizes the evidence of aberrant DOT1L expression and its impact on biological and clinical behavior of breast, ovarian, prostate, colon, and other solid tumors. The structural basis and molecular partners of DOT1L in regulating cell proliferation, invasion, plasticity, stemness, cell-to-cell signaling, epithelial-to-mesenchymal transition, and chemoresistance are also discussed. Moreover, potential therapeutic options targeting DOT1L for the treatment of challenging solid tumors are explored.
FRONTIERS IN GENETICS
(2022)
Article
Cell Biology
Renxian Wang, Dingding Wang, Xueshan Bai, Jianxun Guo, Songxia Xia, Yuning Cheng, Yani Gu, Qian Wang, Jingjun Nie, Dafu Chen, Weifeng Liu, Junbo Liang
Summary: Using CRISPR-Cas9 knockout screens, we identified Polo-like kinase 1 (PLK1) as a specific and essential kinase for the survival and growth of osteosarcoma cells. Knockout of PLK1 inhibited proliferation of osteosarcoma cells in vitro and tumor growth in vivo. The PLK1 inhibitor Volasertib effectively inhibited the growth of osteosarcoma cells in vitro and disrupted tumor development in vivo, primarily through cell-cycle arrest and apoptosis triggered by DNA damage. Our findings provide important insights into the effectiveness and mode of action of PLK1 inhibitors in treating osteosarcoma.
CELL DEATH DISCOVERY
(2023)
Article
Pharmacology & Pharmacy
Ying Xia, Yong Jin, Daxiang Cui, Xia Wu, Cunfeng Song, Weilin Jin, Hai Huang
Summary: Gasdermin E (GSDME) expression is silenced in gastric cancer (GC) due to promoter hypermethylation, and reactivation of GSDME expression can enhance tumor inhibition effects. This study reveals a potential therapeutic strategy against GC by inducing cancer cell-specific pyroptosis through reactivating GSDME expression.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Changwu Wu, Siming Gong, Yingjuan Duan, Chao Deng, Sonja Kallendrusch, Laura Berninghausen, Georg Osterhoff, Nikolas Schopow
Summary: This study aimed to establish a prognostic index (TMEindex) for osteosarcoma based on the tumor microenvironment (TME), to predict patient survival and response to immune checkpoint inhibitor (ICI) therapy. The TMEindex was constructed using the ESTIMATE algorithm and validated in three independent datasets. It was found to be a promising biomarker for prognosis and response to ICI therapy in osteosarcoma.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Shiyu Zhang, Pei Zhou, Jingming Liu, Anjie Xia, Guifeng Lin, Zhiyu Xiang, Zhen Fang, Xin Yang, Jingxin Qiao, Qian Hu, Jiahao Zhang, Jinlong Zhao, Linli Li
Summary: In this study, a new series of ATM kinase inhibitors was reported, which showed promising potential in enhancing the sensitivity of cancer cells to radiotherapy and chemotherapy. A011, one of the most potent inhibitors, exhibited an IC50 value of 1.0 nM against ATM. Experimental results demonstrated that A011 could inhibit activation of the ATM signaling pathway and increase the sensitivity of colorectal cancer cells to irinotecan and ionizing radiation.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Oncology
Ziyi Wang, Renxiang Jia, Linlin Wang, Qiwei Yang, Xiaohai Hu, Qiang Fu, Xinyu Zhang, Wenya Li, Yi Ren
Summary: Defects in DNA repair pathways are common in cancer and have significant impact on tumor metabolism, metastasis, and drug resistance. Rad51 recombinase, upregulated in many malignant tumors, plays a critical role in these processes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shao-Wei Feng, Pei-Chi Chang, Hsuan-Yu Chen, Dueng-Yuan Hueng, Yao-Feng Li, Shih-Ming Huang
Summary: Metformin has been shown to effectively reduce cell proliferation and migration, promote cell apoptosis, and disrupt mitochondrial metabolism in glioblastoma cells. Additionally, the combination treatment of metformin and temozolomide has different effects on glioblastoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Iredia D. Iyamu, Ayad A. Al-Hamashi, Rong Huang
Summary: In this study, a potent pan-inhibitor II757 for PRMTs was designed and synthesized, showing high inhibition for various PRMTs and competitively binding at the SAM binding site of PRMT1. II757 also exhibited selectivity for PRMTs over other methyltransferases, serving as a general probe and a lead for further optimization.
Article
Chemistry, Analytical
Mingmin Wu, Mengtian Zhang, Zhiwei Fan, Xinyue Qin, Xiaoxia Zhu, Haiwei Ji, Yuling Qin, Qi Wang, Li Wu
Summary: Sensitive detection of DNA methyltransferase activity using a new fluorescence transducer based on Forster resonance energy transfer (FRET) is presented, with high analytical performance and capability for enzyme inhibitor screening. The method offers a promising strategy for high-performance diagnosis, drug discovery, and treatment effectiveness evaluation in various disease-related methyltransferase activities.
Article
Chemistry, Inorganic & Nuclear
Jiyong Hu, Tingting Chao, Bangpeng Yuan, Yan Guo, Junshuai Zhang, Jin'an Zhao, Xuemin Zhao, Hongwei Hou
Summary: The copper complexes based on benzimidazole-quinoline exhibited strong antitumor abilities, DNA binding leading to oxidative damage, and induction of apoptosis in HCT116 cells. The generation of reactive oxygen species (ROS) may be a major contributor to apoptotic death in HCT116 cells.
Review
Cell Biology
Irene Yu, Anthony Dakwar, Kazuaki Takabe
Summary: Immunotherapy has shown significant progress in the treatment of colorectal cancer (CRC) in the past decade. Immune checkpoint inhibitors have been particularly effective in improving patient outcomes in a specific subset of CRC. The efficacy and timing of immunotherapy for other subsets of CRC have gained attention, and this review discusses the latest advances and future directions for three main classes of immunotherapy for CRC: immune checkpoint inhibitors, adoptive cell transfer therapy, and tumor vaccines.
Article
Chemistry, Medicinal
Beatrice Noce, Elisabetta Di Bello, Clemens Zwergel, Rossella Fioravanti, Sergio Valente, Dante Rotili, Andrea Masotti, Mohammad Salik Zeya Ansari, Daniela Trisciuoglio, Alokta Chakrabarti, Christophe Romier, Dina Robaa, Wolfgang Sippl, Manfred Jung, Cecile Haeberli, Jennifer Keiser, Antonello Mai
Summary: Schistosoma mansoni HDAC8 is a reliable target for combating schistosomiasis, but most inhibitors lack selectivity over human deacetylases and have low or no activity against the parasite. In this study, a small library of HDAC inhibitors from the lab was tested for their in vitro enzyme and biological activity. These inhibitors showed submicromolar/nanomolar potency against smHDAC8 and varied selectivity over hHDAC1 and/or hHDAC6. Some compounds exhibited high activity against larval and adult stages of S. mansoni with moderate to no toxicity in human fibroblast cells.
Review
Pharmacology & Pharmacy
Clemens Zwergel, Rossella Fioravanti, Antonello Mai
Summary: Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that, when overexpressed, induces an inhibitory signal causing T cell exhaustion and immune escape in tumors. Immunotherapy targeting the PD-L1 pathway has successfully treated various cancers. Recent advances in understanding the complex biology of PD-L1 have led to the development of small-molecule inhibitors. This review highlights the most promising recent advances in understanding the regulation mechanisms of PD-L1 and the use of small-molecule modulators in combination therapy with other epigenetic chemotherapeutic agents.
DRUG DISCOVERY TODAY
(2023)
Article
Oncology
Emanuela Palmerini, Marco Gambarotti, Antoine Italiano, Michael J. Nathenson, Ravin Ratan, Palma Dileo, Salvatore Provenzano, Robin L. Jones, Steven G. DuBois, Javier Martin-Broto, Enrique de Alava, Giacomo G. Baldi, Giovanni Grignani, Virginia Ferraresi, Antonella Brunello, Luca Paoluzzi, Rossella Bertulli, Nadia Hindi, Michael Montemurro, Christian Rothermundt, Stefania Cocchi, Carmen Salguero-Aranda, Davide Donati, Juan D. Martin, Amr H. Abdelhamid Ahmed, Alessandro Mazzocca, Elisa Carretta, Marilena Cesari, Michela Pierini, Alberto Righi, Marta Sbaraglia, Maria A. Laginestra, Katia Scotlandi, Angelo P. Dei Tos, Toni Ibrahim, Silvia Stacchiotti, Bruno Vincenzi
Summary: This study aimed to define the clinical characteristics, treatment, and outcome of undifferentiated small round cell sarcomas (URCSs) patients. The results showed significant differences in prognosis between URCS subtypes, and a full molecular assessment is needed to confirm the diagnosis. Prospective studies are needed to determine the optimal treatment strategy for each URCS subtype.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Chemistry, Medicinal
Elisabetta Di Bello, Veronica Sian, Giulio Bontempi, Clemens Zwergel, Rossella Fioravanti, Beatrice Noce, Carola Castiello, Stefano Tomassi, Davide Corinti, Daniela Passeri, Roberto Pellicciari, Ciro Mercurio, Mario Varasi, Lucia Altucci, Marco Tripodi, Raffaele Strippoli, Angela Nebbioso, Sergio Valente, Antonello Mai
Summary: After years of research, HDAC inhibitors have been developed and approved by FDA/Chinese FDA for the treatment of cancer and non-cancer diseases. A series of novel compounds have been discovered to be effective anticancer agents, demonstrating selective inhibition of HDACs and inducing cell death and differentiation. These compounds also modulate gene and protein expression related to apoptosis and show potent antiproliferative activity in various cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Claudia Maria Hattinger, Iris Chiara Salaroglio, Leonardo Fantoni, Martina Godel, Chiara Casotti, Joanna Kopecka, Katia Scotlandi, Toni Ibrahim, Chiara Riganti, Massimo Serra
Summary: In order to improve the prognosis and cure rate of high-grade osteosarcomas (HGOSs), immune-based treatment approaches, especially for metastatic, relapsed and refractory HGOS patients, have been considered. This review provides an overview of immunotherapeutic treatments targeting, counteracting or exploiting the different immune cell compartments present in the HGOS tumor microenvironment. The strategies and possible mechanisms of HGOS cells to escape these treatments are discussed, as well as ongoing immune-based trials and recent clinical study results.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Francesco Fiorentino, Martina Menna, Dante Rotili, Sergio Valente, Antonello Mai
Summary: RNA methylation is a crucial mechanism for regulating gene expression and RNA maturation. METTL3, an RNA methyltransferase, plays a key role in this process by adding a methyl group to N6-adenosine of RNA. Dysregulation of METTL3 can lead to various diseases and viral infections. By studying the correlation between METTL3 and diseases, as well as analyzing the development and mode of action of known METTL3 inhibitors, we can gain a better understanding of the biological functions of this enzyme and potentially develop new therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Nutrition & Dietetics
Sara Salucci, Alberto Bavelloni, Anna Bartoletti Stella, Francesco Fabbri, Ivan Vannini, Manuela Piazzi, Karyna Volkava, Katia Scotlandi, Giovanni Martinelli, Irene Faenza, William Blalock
Summary: Approximately 7% of childhood cancers and 1% of adult cancers are soft tissue sarcomas, with rhabdomyosarcoma being the most common subtype. Despite current therapeutic protocols, survival rates for RMS have not improved significantly in the past decade. Curcumin, derived from the Curcuma longa plant, has low toxicity and has shown anti-tumorigenic effects in vitro. This study evaluated curcumin's activity in RMS cell lines and identified the major pathways affected by curcumin's anti-tumorigenic effects. Curcumin treatment resulted in cell cycle arrest, inhibited migration and colony formation, and induced apoptosis. Proteome profiler analysis revealed that curcumin primarily influenced signaling through AKT-mTOR, STAT, AMPK, and p53 pathways in a subtype-specific manner. Combinational therapeutic targeting of these pathways may be the best option for RMS treatment.
Review
Oncology
Lorena Landuzzi, Francesca Ruzzi, Pier-Luigi Lollini, Katia Scotlandi
Summary: Synovial sarcoma is a rare malignant tumor characterized by t(X;18) translocation encoding the SS18-SSX fusion gene, which interacts with BAF enhancer and polycomb repressor complexes to regulate gene transcription. Different experimental in vivo models for synovial sarcoma research include transgenic mouse models, patient-derived xenografts, and cell lines. These models have contributed to identifying vulnerabilities and developing new therapies for synovial sarcoma.
Article
Biology
Federica Scotto di Carlo, Sharon Russo, Francesc Muyas, Maria Mangini, Lorenza Garribba, Laura Pazzaglia, Rita Genesio, Flavia Biamonte, Anna Chiara De Luca, Stefano Santaguida, Katia Scotlandi, Isidro Cortes-Ciriano, Fernando Gianfrancesco
Summary: Profilin 1, encoded by PFN1, is a protein that plays a tumor suppressive role in various adenocarcinomas and pagetic osteosarcomas. However, its exact contribution to tumor development is not fully understood. This study shows that inactivation of Profilin 1 leads to multiple mitotic defects, resulting in chromosomal instability and genome rearrangements in pagetic osteosarcomas. Mechanistically, Profilin 1 is involved in regulating cell division and its deficiency impairs actin filament supply during cytokinesis.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Medicinal
Clemens Zwergel, Michele Aventaggiato, Sabrina Garbo, Elisabetta Di Bello, Bruno Fassari, Beatrice Noce, Carola Castiello, Chiara Lambona, Federica Barreca, Dante Rotili, Rossella Fioravanti, Thomas Schmalz, Michael Weyand, Amelie Niedermeier, Marco Tripodi, Gianni Colotti, Clemens Steegborn, Cecilia Battistelli, Marco Tafani, Sergio Valente, Antonello Mai
Summary: The mitochondrial protein SIRT3 plays a role in cancer, metabolism, and hypoxia-related diseases. New 1,4-dihydropyridine compounds, namely 2 and 3, have been discovered and compound 3 is a specific activator of SIRT3. Among a series of related compounds, compound 3c binds and activates SIRT3 the strongest, while compound 3d shows the best effects on enhancing glutamate dehydrogenase activity and deacetylating proteins in breast cancer cells. Compound 3d also exhibits significant anti-cancer effects in both normoxia and hypoxia conditions, reducing cell viability, clonogenicity, and migration ability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Joana Reis, Christoph Gorgulla, Marta Massari, Sara Marchese, Sergio Valente, Beatrice Noce, Lorenzo Basile, Ricarda Toerner, Huel Cox, Thibault Viennet, Moon Hee Yang, Melissa M. Ronan, Matthew G. Rees, Jennifer A. Roth, Lucia Capasso, Angela Nebbioso, Lucia Altucci, Antonello Mai, Haribabu Arthanari, Andrea Mattevi
Summary: In this study, the authors validate inhibitors for human NOX enzymes using computational and experimental methods, opening avenues for cancer drug development and research in redox biology.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Oncology
Lorena Landuzzi, Maria Cristina Manara, Laura Pazzaglia, Pier-Luigi Lollini, Katia Scotlandi
Summary: Synovial sarcoma (SyS) is a rare aggressive soft tissue sarcoma with a unique genetic signature. The majority of patients are initially diagnosed with localized disease, but metastatic relapse is common and advanced stages have a poor prognosis. This review summarizes current treatments and highlights the potential of new epigenetic and immunological strategies. Accurate patient selection based on genetic and tumor immune microenvironment signatures is crucial.
Review
Biochemistry & Molecular Biology
Francesca Ruzzi, Maria Sofia Semprini, Laura Scalambra, Arianna Palladini, Stefania Angelicola, Chiara Cappello, Olga Maria Pittino, Patrizia Nanni, Pier-Luigi Lollini
Summary: Cancer vaccines are being studied to prevent and treat cancers. Prophylactic vaccines for virus-caused cancers are already approved and used globally, while therapeutic cancer vaccines still need further development. Virus-like particles (VLPs) are protein structures designed to mimic viruses and can trigger immune responses. This review provides an overview of preventive VLP-based vaccines approved worldwide for HBV and HPV infections, and evaluates their effectiveness in preventing virus-caused cancers. It also summarizes preclinical and early clinical data on VLP-based cancer vaccines, focusing on HER-2-positive breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)