Article
Chemistry, Medicinal
Martina Menna, Francesco Fiorentino, Biagina Marrocco, Alessia Lucidi, Stefano Tomassi, Domenica Cilli, Mauro Romanenghi, Matteo Cassandri, Silvia Pomella, Michele Pezzella, Donatella Del Bufalo, Mohammad Salik Zeya Ansari, Nevena Tomasevic, Milan Mladenovic, Monica Viviano, Gianluca Sbardella, Rossella Rota, Daniela Trisciuoglio, Saverio Minucci, Andrea Mattevi, Dante Rotili, Antonello Mai
Summary: Chemical modifications of LSD1 led to highly active and selective inhibitors, which showed antiproliferative effects and gene expression regulation in leukemia cells. The inhibition of LSD1 demonstrated a crucial role in solid tumor cells, suggesting no added value for simultaneous G9a inhibition.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Catherine M. Mills, Jonathan Turner, Ivett C. Pina, Kathleen A. Garrabrant, Dirk Geerts, Andre S. Bachmann, Yuri K. Peterson, Patrick M. Woster
Summary: LSD1, an epigenetic regulator, is an oncogenic accomplice in MYCN-expressing neuroblastoma. We report 3 novel scaffolds for reversible LSD1 inhibition and found one of them to be highly potent and able to increase an important modification mark in cells. Combination treatment with bortezomib also showed a synergistic effect.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Baohui Yuan, He Liu, Xiaohua Pan, Xiaoliang Dong, Le-Feng Qu, Jia Sun, Li-Long Pan
Summary: LSD1 plays a crucial role in neointima formation, and its overexpression is associated with neointima formation. Knockdown of LSD1 significantly reduces neointima formation and inhibits platelet-derived growth factor-induced VSMC proliferation. Moreover, LSD1 overexpression exhibits opposite effects in vivo and in vitro.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Cheng Zeng, Jiwei Chen, Emmalee W. Cooke, Arijita Subuddhi, Eliana T. Roodman, Fei Xavier Chen, Kaixiang Cao
Summary: This study reveals the catalytic-independent role of LSD1 in regulating gene expression and cellular differentiation, demonstrating that the loss of LSD1 protein globally de-represses enhancers and impairs cell fate transition. The researchers found that the increase of H3K27ac catalyzed by P300/CBP, rather than the loss of CoREST complex components from chromatin, contributes to the transcription de-repression of LSD1 targets and differentiation defects caused by LSD1 loss.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Jingjing Wang, Zhikai Wu, Xingyi Zhu, Peixuan Li, Yiwu Fu, Xia Wang, Youpeng Sun, Ershun Zhou, Zhengtao Yang
Summary: The study demonstrates the important regulatory roles of LSD1 in LPS-induced mastitis and the inhibitory effects of GSK-LSD1 on LSD1 activity, leading to reduced inflammatory response and tissue damage. The inhibition of LSD1 results in increased histone H3K4me2 and H3K9me2 levels, and suppression of NF-kappa B signaling and cytokine production in mammary gland. These findings suggest LSD1 as a potential regulator of inflammation and provide insights into epigenetic control mechanisms in inflammation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Xing-Jie Dai, Li-Juan Zhao, Long-Hua Yang, Ting Guo, Lei-Peng Xue, Hong-Mei Ren, Zhi-Li Yin, Xiao-Peng Xiong, Ying Zhou, Shi-Kun Ji, Hui-Min Liu, Hong-Min Liu, Ying Liu, Yi-Chao Zheng
Summary: In this study, the antipsychotic drug chlorpromazine was identified as an LSD1 inhibitor, and a series of chlorpromazine derivatives were synthesized. Among them, compound 3s showed the most potent inhibitory activity. Compound 3s inhibited LSD1 at the cellular level, downregulated PD-L1 expression in gastric cancer cells, and enhanced T-cell killing response. Animal studies confirmed that compound 3s can inhibit gastric cancer cell proliferation without significant toxicity in immunocompetent mice. These findings suggest that compound 3s may serve as a lead compound for further development to activate T-cell immunity in gastric cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Hongxiao Wang, Zijun Song, Enjun Xie, Junyi Chen, Biyao Tang, Fudi Wang, Junxia Min
Summary: The combination of inhibiting LSD1 and G9a effectively suppresses cell growth in esophageal squamous cell carcinoma and reduces tumor growth. Clinical studies have shown that LSD1 and G9a are upregulated in cancer tissues and are significantly associated with poor prognosis. Inhibiting LSD1 and G9a induces cell death through S-phase arrest and apoptosis, and cotargeting ER stress pathways enhances this effect.
Article
Multidisciplinary Sciences
Mattie J. Casey, Alexandra M. Call, Annika V. Thorpe, Cicely A. Jette, Michael E. Engel, Rodney A. Stewart
Summary: Lsd1/Kdm1a functions as both a histone demethylase enzyme and a scaffold for assembling chromatin modifier and transcription factor complexes to regulate gene expression during embryogenesis. Our analysis of zebrafish lsd1/kdm1a mutants reveals that Lsd1's scaffolding function, mediated by its SNAG-binding domain, is required for repression of gene expression, including gfi1 and snai1/2, through a negative feedback loop.
Article
Cell Biology
Georgia Papadopoulou, Stavroula Petroulia, Eirini Karamichali, Alexios Dimitriadis, Dimitrios Marousis, Elisavet Ioannidou, Panagiota Papazafiri, John Koskinas, Pelagia Foka, Urania Georgopoulou
Summary: Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. Lysine-specific demethylase 1 (LSD1) is an epigenetic controller of critical cellular functions that are essential for HCV propagation. This study investigates the role of LSD1 in HCV infection and shows that LSD1 overexpression inhibits HCV replication, while inhibition of LSD1 increases viral replication. The study also suggests that LSD1 participates in an antiviral mechanism by activating IFITM3 via demethylation, leading to degradation of HCV virions.
Article
Biochemistry & Molecular Biology
Nao Yamakado, Satoshi Okuda, Kei Tobiume, Ryo Uetsuki, Shigehiro Ono, Kuniko Mizuta, Takayuki Nakagawa, Tomonao Aikawa
Summary: Oral squamous cell carcinoma (SCC) is a tumor with bidirectional cell plasticity, and the chemical LSD1 inhibitor can induce EMT in the cell line OM-1. The induction of EMT is associated with the upregulation of EMT-TFs ZEB1 and Snail, as well as increased histone H3 methylation in the regulatory regions of ZEB1.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Neurosciences
Chiara Forastieri, Maria Italia, Emanuela Toffolo, Elena Romito, Maria Paola Bonasoni, Valeria Ranzani, Beatrice Bodega, Francesco Rusconi, Elena Battaglioli
Summary: The recent branching of the mammalian evolutionary tree has led to increased brain complexity and vulnerability of emotional circuitry. A study found a restricted interaction between RbFOX1 and LSD1 in higher primates, suggesting an evolutionary recent pathway related to psychiatric disorders. RbFOX1 is also involved in regulating LSD1 and immediate early genes, providing additional insights into its role in stress response.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Shan Hu, Peng Cao, Kangle Kong, Peng Han, Yu Deng, Fan Li, Bo Zhao
Summary: In this study, it was found that miR-449a delays lung cancer development through suppressing the KDM3A/HIF-1 alpha axis. MiR-449a interacts with KDM3A, while HIF-1 alpha can bind with KDM3A. Up-regulating miR-449a inhibits lung cancer development, while up-regulating KDM3A promotes cellular aggression. Restoring miR-449a impairs tumorigenesis in vivo in lung cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Review
Oncology
Emily E. Hartung, Kanwaldeep Singh, Tobias Berg
Summary: Acute Myeloid Leukemia (AML) is a heterogeneous cancer of the blood system where mutations in myeloid transcription factors and epigenetic regulators contribute to the disease pathogenesis. Inhibition of LSD1, an epigenetic regulator, shows promise in restoring differentiation in AML. The modulation of transcription factor networks by LSD1 inhibition is different between normal and malignant hematopoiesis, offering potential for combination therapies.
FRONTIERS IN ONCOLOGY
(2023)
Review
Cell Biology
Carlos Martinez-Gamero, Sandhya Malla, Francesca Aguilo
Summary: This review summarizes the current knowledge about LSD1 and its molecular mechanism in influencing the stem cell state, including the regulatory circuitry underlying self-renewal and pluripotency.
Article
Chemistry, Medicinal
M. Naveen Sadhu, Dhanalakshmi Sivanandhan, Chandru Gajendran, Subramanyam Tantry, Purushottam Dewang, Kannan Murugan, Srinatha Chickamunivenkatappa, Mohd Zainuddin, Sreekala Nair, Krishnakumar Vaithilingam, Sridharan Rajagopal
Summary: The article introduces a novel LSD1 and HDAC6 dual inhibitor, which has shown good efficacy in multiple myeloma in experiments, providing a new treatment strategy for various cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Oncology
Milena Perrone, Claudia Chiodoni, Mara Lecchi, Laura Botti, Barbara Bassani, Annamaria Piva, Elena Jachetti, Matteo Milani, Daniele Lecis, Elda Tagliabue, Paolo Verderio, Sabina Sangaletti, Mario P. Colombo
Summary: Cancer can reprogram the bone marrow niche through the BM mesenchymal stem cells (MSC) and IL-1B/ATF3 signaling pathway, which promotes myeloid cell differentiation and tumor development. The expression of CD11b thorn population in the peripheral blood can be used as a potential biomarker for early diagnosis of breast cancer. This study suggests that targeting IL-1B or ATF3 may have therapeutic benefits for breast cancer patients.
Article
Oncology
Riccardo Ray Colciago, Irene Fischetti, Carlotta Giandini, Eliana La Rocca, Tiziana T. Rancati, Alicia Rejas Mateo, Mario Paolo Colombo, Laura Lozza, Claudia Chiodoni, Elena Jachetti, Maria Carmen De Santis
Summary: Oncological treatments are rapidly changing with the introduction of targeted anticancer drugs and regimens, and radioimmunotherapy is emerging as a promising field. This review provides an overview of the synergistic use of radiotherapy and immunotherapy and addresses important questions about its implementation, the patient selection criteria, and when it becomes standard clinical practice.
EXPERT REVIEW OF ANTICANCER THERAPY
(2023)
Article
Oncology
Eleonora Cesari, Alessandra Ciucci, Marco Pieraccioli, Cinzia Caggiano, Camilla Nero, Davide Bonvissuto, Francesca Sillano, Marianna Buttarelli, Alessia Piermattei, Matteo Loverro, Floriana Camarda, Viviana Greco, Maria De Bonis, Angelo Minucci, Daniela Gallo, Andrea Urbani, Giuseppe Vizzielli, Giovanni Scambia, Claudio Sette
Summary: High grade serous ovarian cancer (HGSOC) is a highly lethal form of cancer, and there is a need for targeted therapies and overcoming chemotherapy resistance. CDK12 and CDK13 have been identified as potential therapeutic targets in HGSOC, but their effects and potential synergy with other drugs are not well understood.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Elisa Bianchi, Sebastiano Rontauroli, Lara Tavernari, Margherita Mirabile, Francesca Pedrazzi, Elena Genovese, Stefano Sartini, Massimiliano Dall'Ora, Giulia Grisendi, Luca Fabbiani, Monica Maccaferri, Chiara Carretta, Sandra Parenti, Sebastian Fantini, Niccolo Bartalucci, Laura Calabresi, Manjola Balliu, Paola Guglielmelli, Leonardo Potenza, Enrico Tagliafico, Lorena Losi, Massimo Dominici, Mario Luppi, Alessandro Maria Vannucchi, Rossella Manfredini
Summary: BM fibrosis is a major pathology in myelofibrosis and is associated with overexpression of OPN protein. ERK1/2 is a key regulator of OPN production, and inhibiting ERK1/2 activity can reduce OPN production and hinder the development of BM fibrosis. Targeting OPN and ERK1/2 could be potential therapeutic strategies for myelofibrosis.
Article
Oncology
Bianca Cioni, Silvia Ratti, Annamaria Piva, Irene Tripodi, Matteo Milani, Francesca Menichetti, Tiziana Langella, Laura Botti, Loris De Cecco, Claudia Chiodoni, Daniele Lecis, Mario P. Colombo
Summary: Breast cancer, especially the luminal subtype, is a common and threatening disease due to therapy resistance. JMJD6, known for its epigenetic activity, is found to have a negative prognostic value in luminal breast cancer and can regulate cancer cell pathways. This study discovers a novel function of JMJD6, showing that its genetic inhibition in breast cancer cells reduces lipid droplet formation and ANXA1 expression, ultimately preventing tumor aggressiveness by inhibiting M2-type macrophage polarization in the tumor microenvironment.
MOLECULAR CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Valentina Panzeri, Marco Pieraccioli, Eleonora Cesari, Pierre de la Grange, Claudio Sette
Summary: Transcription-associated cyclin-dependent kinases (CDKs) regulate the transcription cycle through phosphorylation of RNA polymerase II (RNAPII). This study found that inhibiting CDK12 and CDK13 impaired splicing of specific promoter-proximal introns. The inhibition of CDK12/13 disrupted the interaction between SF3B1 and RNAPII, resulting in retention of these introns and a synergistic effect with another inhibitor on cell survival and cancer progression.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Mila Gugnoni, Eugenia Lorenzini, Italo Faria do Valle, Daniel Remondini, Gastone Castellani, Federica Torricelli, Elisabetta Sauta, Benedetta Donati, Moira Ragazzi, Francesco Ghini, Simonetta Piana, Alessia Ciarrocchi, Gloria Manzotti
Summary: This study validated specific gene signatures in the transition from differentiated thyroid carcinoma (DTC) to anaplastic thyroid cancer (ATC) and identified the E2F7 gene as a key player in this process. Down-regulation of E2F7 reduced the aggressiveness of ATC cells.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Federica Torricelli, Elisabetta Sauta, Veronica Manicardi, Vincenzo Dario Mandato, Andrea Palicelli, Alessia Ciarrocchi, Gloria Manzotti
Summary: This study identified potential drug candidates for high-risk endometrial cancer using a computational drug repurposing approach.
Article
Oncology
Caterina Cascini, Chiara Ratti, Laura Botti, Beatrice Parma, Valeria Cancila, Adriana Salvaggio, Cristina Meazza, Claudio Tripodo, Mario P. Colombo, Claudia Chiodoni
Summary: Osteosarcoma (OS) is the most common primary bone tumor in children and adolescent. In this study, it was found that intralesional administration of a TLR9 agonist can effectively inhibit tumor growth and also have therapeutic effects on untreated contralateral lesions. The findings suggest that TLR9 agonist can act as an in situ anti-tumor vaccine, activating innate and adaptive immune responses to suppress tumor growth.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Veronica Manicardi, Mila Gugnoni, Elisabetta Sauta, Benedetta Donati, Emanuele Vitale, Federica Torricelli, Gloria Manzotti, Simonetta Piana, Caterina Longo, Francesco Ghini, Alessia Ciarrocchi
Summary: Mortality from vmelanoma is associated with metastatic disease, but the mechanisms leading to spreading of the cancer cells remain obscure. Spatial profiling revealed that melanoma is characterized by a high degree of heterogeneity, which is established by the ability of melanoma cells to switch between different phenotypical stages. This plasticity, likely a heritage from embryonic pathways, accounts for a relevant part of the metastatic potential of these lesions, and requires the rapid and efficient reorganization of the transcriptional landscape of melanoma cells.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
S. Cortellino, V. Quagliariello, G. Delfanti, O. Blazevits, C. Chiodoni, N. Maurea, A. Di Mauro, F. Tatangelo, F. Pisati, A. Shmahala, S. Lazzeri, V. Spagnolo, E. Visco, C. Tripodo, G. Casorati, P. Dellabona, V. D. Longo
Summary: This study explores the use of periodic cycles of a fasting-mimicking diet (FMD) to reduce the side effects caused by immunotherapy in cancer treatment. The combination of FMD cycles with immunotherapy shows promising results in delaying cancer growth and reducing cardiotoxicity.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Magda Zanelli, Francesca Sanguedolce, Maurizio Zizzo, Valentina Fragliasso, Giuseppe Broggi, Andrea Palicelli, Giuseppe Gaetano Loscocco, Camilla Cresta, Cecilia Caprera, Matteo Corsi, Giovanni Martino, Alessandra Bisagni, Marialisa Marchetti, Nektarios Koufopoulos, Paola Parente, Rosario Caltabiano, Stefano Ascani
Summary: This paper focuses on the clinical and pathological features of lymphoblastic lymphoma of B- or T-cell origin and mantle cell lymphoma, particularly its blastoid variant, involving the skin. It emphasizes the importance of precise diagnosis for different diseases with similar blastic characteristics that have different outcomes and require distinct therapeutic strategies in patient management. The assessment of skin biopsies of hematological neoplasms with blastic features poses diagnostic challenges and requires consideration of a wide range of differential diagnoses.
Review
Oncology
Claudia Piombino, Marco Oltrecolli, Elena Tonni, Marta Pirola, Rossana Matranga, Cinza Baldessari, Stefania Pipitone, Massimo Dominici, Roberto Sabbatini, Maria Giuseppa Vitale
Summary: De novo metastatic hormone-sensitive prostate cancer usually has a poor prognosis, but recent advancements in new hormonal agents and combination therapy have slightly improved outcomes. Ongoing clinical trials are exploring new therapeutic approaches and personalized treatment options based on genomic features and biomarker-guided treatment.
Article
Oncology
C. Chiodoni, S. Sangaletti, M. Lecchi, C. M. Ciniselli, V Cancila, I. Tripodi, C. Ratti, G. Talarico, S. Brich, L. De Cecco, P. Baili, M. Truffi, F. Sottotetti, F. Piccotti, C. Tripodo, G. Pruneri, T. Triulzi, F. Corsi, V Cappelletti, S. Di Cosimo, P. Verderio, M. P. Colombo
Summary: This study identified three genes, CSTB, CCDC91, and ITGB1, associated with early locoregional recurrence (LRR) in luminal-like breast cancer patients. These genes could serve as a useful tool for predicting early recurrence risk and guiding treatment decisions.