Article
Chemistry, Medicinal
Renshuai Zhang, Na Xiao, Qi Xu, Qiuyu Gong, Fandong Kong, Hongfei Jiang
Summary: Mitochondria has been identified as a target for tumor therapy. This study developed a mitochondria-targeting anticancer agent, MT-1, which specifically accumulates in mitochondria and binds to GR. MT-1 damages the morphology and function of mitochondria, inhibits mitochondrial respiration and glycolysis, and binds to a new site of GR to inhibit its activity. This provides a potential novel strategy for tumor therapy by targeting novel sites of GR in mitochondria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Qi-Zhang Li, Zan-Wen Zuo, Ze-Rong Zhou, Yan Ji
Summary: Polyamine metabolism plays a crucial role in anticancer strategies, with combination therapies and effective use of natural active ingredients showing promising results. Polyamine metabolic enzymes are key therapeutic targets, and combination therapies may be more effective than monotherapies based on polyamine depletion.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Cell Biology
Binxiang Chu, Zhenghua Hong, Xiaohe Zheng
Summary: AGK is a recently discovered mitochondrial lipid kinase that plays a crucial role in lipid metabolism stability, mitochondrial protein transport, glycolysis, and thrombocytopoiesis. It has been identified as an oncogene involved in tumor cell growth, invasion, metastasis, and drug resistance, making it a promising target for cancer therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Fenting Lei, Pei Li, Tangting Chen, Qian Wang, Chenglong Wang, Yan Liu, Yiping Deng, Zongquan Zhang, Maochang Xu, Ji Tian, Wei Ren, Chunhong Li
Summary: Curcumin exhibits potent anti-inflammatory and anti-tumor activities, but its poor solubility, stability, and bioavailability limit its therapeutic potential. Nanoparticle delivery systems can improve these limitations and enhance targeting. However, the immune system easily clears exogenous nanoparticles, necessitating the development of biomimetic nanomedicines with good biocompatibility and long circulation time.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Octavia Cadassou, Lars Petter Jordheim
Summary: More and more studies are focusing on the complex metabolic characteristics and plasticity of cancer cells. New metabolism-targeting therapeutic strategies, including classical and promising OXPHOS inhibitors (OXPHOSi), are being developed to address these specificities and vulnerabilities. OXPHOSi show limited efficiency as monotherapy but have potential in combination with conventional therapeutic strategies and other innovative approaches.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Somarupa Sahoo, Abinaya Raghavan, Arun Kumar, Dipankar Nandi, Akhil R. Chakravarty
Summary: Iron(III) complexes of curcumin with tridentate NNN-donor dipicolylamine-based ligands were prepared and studied for their photo-induced cytotoxicity in cancer cell lines. The biotinylated analogue of the complex showed enhanced cellular uptake and cytotoxicity, making it a potential targeted photodynamic therapy drug.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Article
Oncology
Tomo Ishida, Tsuyoshi Takahashi, Yukinori Kurokawa, Toshirou Nishida, Seiichi Hirota, Satoshi Serada, Minoru Fujimoto, Tetsuji Naka, Ryugo Teranishi, Takuro Saito, Kotaro Yamashita, Koji Tanaka, Kazuyoshi Yamamoto, Tomoki Makino, Makoto Yamasaki, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki
Summary: This study revealed metabolic changes and sensitivity to the GPX4 inhibitor RSL3 in imatinib-derived persister GIST cells, as well as the iron-dependent and caspase-independent cell death induced by RSL3. Additionally, the combination of RSL3 with TKI showed promise in inhibiting tumour regrowth in both GIST and epidermal growth factor receptor-mutated lung cancer.
BRITISH JOURNAL OF CANCER
(2021)
Article
Veterinary Sciences
Luqiu Feng, Guodong Luo, Yuhang Li, Chen Zhang, Yuxuan Liu, Yanqing Liu, Hongyue Chen, Daoling He, Yan Zhu, Ling Gan
Summary: This study demonstrated that curcumin (CUR) can promote the polarization of microglia cells from M1 phenotype to M2 phenotype and reverse mitochondrial dysfunction caused by PRV infection. CUR also prevents inflammatory damage by regulating energy metabolism pathway. Furthermore, CUR protects neurons from PRV-induced encephalitis and improves the symptoms associated with viral encephalitis.
VETERINARY RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Valentina Angerilli, Francesca Galuppini, Gianluca Businello, Luca Dal Santo, Edoardo Savarino, Stefano Realdon, Vincenza Guzzardo, Lorenzo Nicole, Vanni Lazzarin, Sara Lonardi, Fotios Loupakis, Matteo Fassan
Summary: The introduction of precision therapies targeting specific gene mutations in neoplasms is revolutionizing oncology, but resistance mechanisms developed by tumors pose challenges to the effectiveness of these drugs over time. Identifying indicators for monitoring and overcoming drug resistance is crucial. MicroRNAs, as stable molecules easily detectable in tissues and biofluids, are ideal biomarkers for identifying patients with resistance to targeted therapies.
Review
Oncology
Sylvain Ladoire, Cedric Rebe, Francois Ghiringhelli
Summary: Immune-checkpoint inhibitors have significantly impacted cancer management, but resistance remains a major issue. To overcome this, combination strategies with other therapies are being explored.
CLINICAL CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Johannes Braegelmann, Carina Lorenz, Sven Borchmann, Kazuya Nishii, Julia Wegner, Lydia Meder, Jenny Ostendorp, David F. Ast, Alena Heimsoeth, Takamasa Nakasuka, Atsuko Hirabae, Sachi Okawa, Marcel A. Dammert, Dennis Plenker, Sebastian Klein, Philipp Lohneis, Jianing Gu, Laura K. Godfrey, Jan Forster, Marija Trajkovic-Arsic, Thomas Zillinger, Mareike Haarmann, Alexander Quaas, Stefanie Lennartz, Marcel Schmiel, Joshua D'Rozario, Emily S. Thomas, Henry Li, Clemens A. Schmitt, Julie George, Roman K. Thomas, Silvia von Karstedt, Gunther Hartmann, Reinhard Buettner, Roland T. Ullrich, Jens T. Siveke, Kadoaki Ohashi, Martin Schlee, Martin L. Sos
Summary: Kinase inhibitors are commonly used in cancer treatment, but resistance can develop. This study explores how activating RIG-I can enhance cancer cell death when combined with kinase inhibition, potentially reducing treatment resistance and promoting tumor shrinkage. By understanding the mechanisms behind intratumoral reprogramming, the efficacy of targeted drugs in genetically defined cancer patients may be prolonged.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Cancan Lyu, Yuanchao Ye, Ronald J. Weigel, Songhai Chen
Summary: This study reveals that targeting Gi/o-GPCR signaling is a promising strategy for eradicating cancer stem cells (CSCs) and enhancing HER2-targeted therapy in breast cancer.
Review
Pharmacology & Pharmacy
Shubhangi Saxena, Neha Dagar, Vishwadeep Shelke, Maciej Lech, Pragyanshu Khare, Anil Bhanudas Gaikwad
Summary: The kidney undergoes metabolic reprogramming in various disease states, and understanding the involved bioenergetic pathways and developing targeted interventions are crucial for addressing the high number of kidney disease cases worldwide. Reprogramming of metabolic pathways has been observed in kidney disease, and therapies targeting these pathways have shown promising results in retarding disease progression. This review focuses on potential pharmacological interventions targeting metabolic reprogramming that have advanced through clinical trials and preclinical studies, with the aim of managing kidney disease effectively in the future.
DRUG DISCOVERY TODAY
(2023)
Article
Microbiology
Stephen E. Noell, Gregory E. Barrell, Christopher Suffridge, Jeff Morre, Kevin P. Gable, Jason R. Graff, Brian J. VerWey, Ferdi L. Hellweger, Stephen J. Giovannoni
Summary: The SAR11 bacteria can uptake and metabolize multiple polyamine compounds, serving as sources of carbon and nitrogen. These polyamines can meet their nitrogen requirements, but cannot fully substitute for the need for glycine or pyruvate. The findings support the hypothesis that enzyme multifunctionality enables streamlined cells in planktonic ecosystems to increase the range of DOM compounds they metabolize.
Review
Pharmacology & Pharmacy
Vahideh Keyvani, Espanta Riahi, Meysam Yousefi, Seyed-Alireza Esmaeili, Rana Shafabakhsh, Amin Moradi Hasan-Abad, Maryam Mahjoubin-Tehran, Michael R. Hamblin, Samaneh Mollazadeh, Hamed Mirzaei
Summary: This article discusses the molecular mechanism of gynecologic cancer and the role of cancer stem cells (CSCs) in treatment, aiming to discover more specific therapeutic approaches to gynecologic cancer.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Hetakshi Kurani, Seyedeh Fatemeh Razavipour, Kuzhuvelil B. Harikumar, Matthew Dunworth, Andrew J. Ewald, Apsra Nasir, Gray Pearson, Derek Van Booven, Zhiqun Zhou, Diana Azzam, Claes Wahlestedt, Joyce Slingerland
Summary: This study identified DOT1L as a key regulator of cancer stem cells (CSCs) in triple-negative breast cancer (TNBC). Inhibition of DOT1L suppressed the growth and metastasis of TNBC CSCs, suggesting that DOT1L inhibitors may be a potential therapeutic option for targeting stem cell-enriched TNBC.
CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Eloise M. Grasset, Matthew Dunworth, Gaurav Sharma, Melanie Loth, Joseph Tandurella, Ashley Cimino-Mathews, Melissa Gentz, Sydney Bracht, Meagan Haynes, Elana J. Fertig, Andrew J. Ewald
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. Our study demonstrates the important and complex role of epithelial-mesenchymal transition (EMT) programs during TNBC metastasis. We observed the presence of a large population of hybrid epithelial-mesenchymal cells in TNBC tumors, which express both epithelial and mesenchymal characteristics and promote invasion in vitro. The mesenchymal marker vimentin promotes invasion and represses metastatic outgrowth. We also identified distinct patterns of EMT transcription factor utilization during invasion and colony formation. Our findings suggest a sequential activation of multiple EMT molecular programs during the metastatic cascade. Longitudinal single-cell RNA analysis detected three different EMT-related molecular patterns, indicating a complex spectrum of epithelial, hybrid E/M, and mesenchymal cell states within metastases. Our results highlight the heterogeneity and multiple molecular strategies for successful distant organ colonization in TNBC.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Maxwell B. Colonna, Tonya Moss, Sneha Mokashi, Sujata Srikanth, Julie R. Jones, Jackson R. Foley, Cindy Skinner, Angie Lichty, Anthony Kocur, Tim Wood, Tracy Murray Stewart, Robert A. Casero, Heather Flanagan-Steet, Arthur S. Edison, Michael J. Lyons, Richard Steet
Summary: Mono- and bi-allelic variants in ALDH18A1 cause a spectrum of human disorders associated with cutaneous and neurological findings that overlap with both cutis laxa and spastic paraplegia. This study characterizes a previously unreported ALDH18A1 variant and identifies alterations in amino acid and antioxidant metabolism. The findings shed new light on the pathogenesis of ALDH18A1-related disorders.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Kamyar Zahedi, Sharon Barone, Marybeth Brooks, Tracy Murray Stewart, Robert A. Casero, Manoocher Soleimani
Summary: This study reveals the metabolic changes and gene expression alterations in TSC renal cystogenesis using a mouse model. The observed changes in the metabolome and transcriptome of Tsc1 KO mice are associated with unregulated cell growth and the presence of A-intercalated cells in renal cysts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tracy Murray Stewart, Jackson R. Foley, Cassandra E. Holbert, Glynis Klinke, Gernot Poschet, Raphael R. Steimbach, Aubry K. Miller, Robert A. Casero Jr
Summary: Cytosolic histone deacetylase-10 (HDAC10) has been found to deacetylate the modified polyamine N8-acetylspermidine (N8-AcSpd) into spermidine, which can support tumor growth, indicating the important role of HDAC10 in cell proliferation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Raphael R. Steimbach, Corey J. Herbst-Gervasoni, Severin Lechner, Tracy Murray Stewart, Glynis Klinke, Johannes Ridinger, Magalie N. E. Geraldy, Gergely Tihanyi, Jackson R. Foley, Ulrike Uhrig, Bernhard Kuster, Gernot Poschet, Robert A. Casero, Guillaume Medard, Ina Oehme, David W. Christianson, Nikolas Gunkel, Aubry K. Miller
Summary: We report the development of a selective chemical probe DKFZ-748 for HDAC10, demonstrating its potency and selectivity through cellular and biochemical assays. The cocrystal structures of our probe with HDAC10 provide a structural basis for its potency, and chemoproteomic profiling confirms its selectivity across the landscape of HDAC drugs. Treatment with DKFZ-748 validates the suspected cellular function of HDAC10 as a polyamine deacetylase, and its dose-dependent growth inhibition in a polyamine-limiting in vitro tumor model shows its potential as a therapeutic agent.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Genetics & Heredity
Steven W. James, Jonathan Palmer, Nancy P. Keller, Morgan L. Brown, Matthew R. Dunworth, Sarah G. Francisco, Katherine G. Watson, Breanna Titchen, Alecia Achimovich, Andrew Mahoney, Joseph P. Artemiou, Kyra G. Buettner, Madelyn Class, Andrew L. Sydenstricker, Sarah Lea Anglin
Summary: This study investigates the role of snxA and gyfA genes in cell cycle regulation in Aspergillus nidulans. The results show that snxA mutations specifically suppress the heat sensitivity of CDK1 pathway mutants, while the deletion and reconstructed allele of gyfA gene can suppress this heat sensitivity. Furthermore, the study reveals the involvement of H3K36 methylation in repressing snxA transcription.
Article
Biochemistry & Molecular Biology
Elodie Henriet, Hildur Knutsdottir, Eloise M. M. Grasset, Matthew Dunworth, Meagan Haynes, Joel S. S. Bader, Andrew J. J. Ewald
Summary: Inter-patient and intra-tumoral heterogeneity makes it difficult to identify predictive biomarkers and effective treatments for basal triple negative breast cancer (b-TNBC). In this study, we cultured organoids from a b-TNBC mouse model and characterized their invasive behavior. By isolating individual organoids from collagen gels based on invasive morphology and performing RNA sequencing, we identified KRAS and ERK as essential regulators of collective and single cell dissemination. Inhibition of EGFR, MAPK/ERK, or PI3K/AKT signaling was found to reduce invasion.
Article
Chemistry, Multidisciplinary
Catherine. M. Mills, Thomas. Z. Benton, Ivett Pina, Megan. J. Francis, Leticia Reyes, Nathan. G. Dolloff, Yuri. K. Peterson, Patrick. M. Woster
Summary: High-risk neuroblastoma accounts for a significant portion of pediatric cancer deaths and there is a need for new and more effective therapeutic approaches. CD38 is a protein that is involved in immunosuppression within the tumor microenvironment. Small molecule inhibitors of CD38 have been identified and shown to have immunomodulatory effects on immune cells in combination with other treatments. These compounds represent a promising novel approach to neuroblastoma immunotherapy.
Article
Medicine, Research & Experimental
Tracy Murray Stewart, Jackson R. Foley, Cassandra E. Holbert, Maxim Khomutov, Noushin Rastkari, Xianzun Tao, Alex R. Khomutov, R. Grace Zhai, Robert A. Casero Jr
Summary: Snyder-Robinson syndrome (SRS) is a genetic disorder caused by mutations in the spermine synthase (SMS) gene, leading to symptoms such as intellectual disability and osteoporosis. Current treatment options focus on managing symptoms. A study has found that the drug 2-difluoromethylornithine (DFMO) can rebalance the spermidine:spermine ratio in SRS patient cells and improve lifespan in a fruit fly model of the syndrome.
EMBO MOLECULAR MEDICINE
(2023)
Article
Genetics & Heredity
Leah R. Padgett, Mollie R. Shinkle, Spencer Rosario, Tracy Murray Stewart, Jackson R. Foley, Robert A. CaseroJr, Myung Hee Park, Wendy K. Chung, Teresa L. Mastracci
Summary: DHPS deficiency is a rare genetic disease caused by mutations in the DHPS gene, resulting in altered protein abundance and impaired enzyme function. These mutations lead to changes in the post-translational modifications of eIF5A, affecting its localization and resulting in developmental and neurological impairments. A mouse model with DHPS deletion in the brain further demonstrates the impact of hypusine biosynthesis loss on neuronal function. This study provides crucial insights into the mechanisms and consequences of DHPS deficiency, aiding in the development of potential treatment strategies.
HUMAN GENETICS AND GENOMICS ADVANCES
(2023)
Meeting Abstract
Oncology
Tracy Murray Stewart, Jackson R. Foley, Patrick M. Woster, Robert A. Casero
Meeting Abstract
Oncology
Cassandra E. Holbert, Jackson R. Foley, Tracy Murray Stewart, Michael J. Walker, Elizabeth Bruckheimer, Jennifer K. Simpson, Robert A. Casero
Meeting Abstract
Oncology
Tracy Murray Stewart, Raphael R. Steimbach, Jackson R. Foley, Aubry K. Miller, Robert A. Casero
Meeting Abstract
Oncology
Tracy Murray Stewart, Raphael R. Steimbach, Jackson R. Foley, Aubry K. Miller, Robert A. Casero
