Review
Immunology
Anne E. O'Shea, Franklin A. Valdera, Daniel Ensley, Todd R. Smolinsky, Jessica L. Cindass, Phillip M. Kemp Bohan, Annelies T. Hickerson, Elizabeth L. Carpenter, Patrick M. McCarthy, Alexandra M. Adams, Timothy J. Vreeland, Guy T. Clifton, George E. Peoples
Summary: Rapamycin inhibits mTOR signaling, exhibiting both immunosuppressive and immunostimulatory effects on innate and adaptive immune responses. The dose and administration schedule play a crucial role in modulating rapamycin's immunologic effects.
CLINICAL IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Douglas R. Wassarman, Kondalarao Bankapalli, Leo J. Pallanck, Kevan M. Shokat
Summary: Mammalian target of rapamycin (mTOR) is a crucial factor in cell growth and metabolism, and its signaling in different tissues affects whole-organism processes. Researchers have developed selecTOR, a chemical-genetic system that restricts the activity of rapamycin analog in specific cell populations, achieving selective mTOR inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Nastaran Daneshgar, Peter S. Rabinovitch, Dao-Fu Dai
Summary: mTOR signaling plays a crucial role in regulating cellular metabolism and aging by controlling key cellular processes such as protein synthesis, autophagy, and mitochondrial function. Dysregulation of mTOR signaling has been associated with various age-related pathologies, including heart failure and age-related cardiac dysfunction.
Review
Biochemistry & Molecular Biology
Wencheng Fu, Geng Wu
Summary: The balance between anabolism and catabolism is disrupted with aging, with mTOR playing a key role in enhancing anabolism and inhibiting catabolism. Downregulation of the mTOR signaling pathway has been found to extend lifespan and mimic the effects of calorie restriction. In addition to anti-aging effects, mTOR signaling has also been implicated in cancer therapy, with rapamycin and rapalogs showing efficacy in certain tumor growth prevention.
Article
Biochemistry & Molecular Biology
R. Mahalakshmi, J. Priyanga, Dipita Bhakta-Guha, Gunjan Guha
Summary: This study demonstrates that low doses of rapamycin can alleviate aging-associated mitochondrial dyshomeostasis in WRL-68 cells, such as oxidative damage to mitochondrial nucleic acids and proteins, as well as imbalance in mitochondrial density, membrane potential, biogenesis, mitophagy, and overall metabolism.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Immunology
Susann Hetze, Lennart Barthel, Laura Luckemann, Hauke S. Gunther, Clemens Wulfing, Yasmin Salem, Marie Jakobs, Tina Horbelt-Grunheidt, Jasmin Petschulat, Ivo Bendix, Ulrike Weber-Stadlbauer, Ulrich Sure, Manfred Schedlowski, Martin Hadamitzky
Summary: This study confirms the efficacy of using taste-immune associative learning with rapamycin in inhibiting GBM tumor growth while promoting the development of an anti-inflammatory anti-tumor microenvironment. These findings can serve as a reference for implementing learning protocols as alternative or supportive treatment strategies in clinical settings.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Review
Chemistry, Medicinal
Shuo Li, Jia-shu Chen, Xiangqian Li, Xiaoyi Bai, Dayong Shi
Summary: Overexpression of eIF4E is common in various solid tumors and hematologic cancers, making it a potential anti-cancer target. This review provides a detailed classification and description of the anti-cancer activities of promising compounds, concluding that MNK1/2 and eIF4E/eIF4G interaction inhibitors are superior to mTOR inhibitors for targeted therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Cell Biology
Yan Zhang, Jinjin Zhang, Shixuan Wang
Summary: Anti-aging is a complex global challenge, and rapamycin can prolong healthy lifespan by inhibiting the mTOR pathway, although current evidence for its effectiveness in lifespan extension is not yet comprehensive. This drug has significant anti-aging effects on multiple organ systems.
AGEING RESEARCH REVIEWS
(2021)
Article
Cell Biology
Sora Kwon, Kiwon Ban, Young-Kwon Hong, Jung-Suk Sung, Inho Choi
Summary: The study demonstrates that rapamycin effectively inhibits the proliferation of hepatocellular carcinoma (HCC) cells and that Prospero-related homeobox 1 (PROX1) plays a key role in the anti-proliferative effect of rapamycin. The increased expression of PROX1 by MTOR inhibition can be used as a useful marker for predicting whether HCC cells can be affected by rapamycin.
Article
Biochemistry & Molecular Biology
Lukas Adam, Megan Stanifer, Fabian Springer, Jan Mathony, Maik Brune, Chiara Di Ponzio, Roland Eils, Steeve Boulant, Dominik Niopek, Stefan M. Kallenberger
Summary: Through integrated analysis, this study reveals the dynamics of the host cell transcriptional response to SARS-CoV-2 infection. The findings provide insights into potential therapeutic targets for inhibiting infection.
Article
Oncology
Zhongbo Liu, Noriko N. Yokoyama, Liankun Song, Jun Xie, Zhina Sadeghi, Yi Xi Wu, Sarah Yee, Xue-Ru Wu, Beverly Wang, Edward Uchio, Xiaolin Zi
Summary: Swedish Herbal Rhodiola-5 (SHR-5) is a standardized Rhodiola Rosea extract that has shown potential in managing depression and fatigue. This study found that daily consumption of SHR-5 significantly improved survival rates and reduced tumor burden in bladder tumor-bearing mice. The mechanism of action is believed to be through the inhibition of mTOR and reshaping of tumor metabolism. These findings suggest that SHR-5 could be a potential anti-aging agent for bladder cancer prevention.
Article
Radiology, Nuclear Medicine & Medical Imaging
Rachelle Durand, Janet R. Reid, Jean B. Belasco, Sphoorti Shellikeri, Juan S. Calle-Toro, Anne Marie Cahill, Abhay Srinivasan
Summary: This study retrospectively characterized changes seen on MRI of children with extensive LMs treated with sirolimus. Significant reductions in volume and signal on T2-weighted MRI were observed with sirolimus treatment, with greater decreases in volume seen in younger children and craniocervical lesions.
AMERICAN JOURNAL OF ROENTGENOLOGY
(2021)
Review
Chemistry, Medicinal
Patrik Oleksak, Eugenie Nepovimova, Zofia Chrienova, Kamil Musilek, Jiri Patocka, Kamil Kuca
Summary: Mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cell functions. Dysregulation of mTOR activity is associated with various pathological conditions. Inhibition of overactivated mTOR is a rational approach for treating human diseases. Rapamycin is a natural inhibitor of mTOR with antitumor and immunosuppressive activity. Different generations of mTOR inhibitors have been developed, including rapalogs, mTOR kinase inhibitors, and dual PI3K/mTOR inhibitors. Novel inhibitors are still being developed to better understand the role of mTOR in signaling pathways and human diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Geriatrics & Gerontology
Zofia Chrienova, David Rysanek, Patrik Oleksak, Dorota Stary, Marek Bajda, Milan Reinis, Romana Mikyskova, Ondrej Novotny, Rudolf Andrys, Adam Skarka, Pavla Vasicova, Josef Novak, Martin Valis, Kamil Kuca, Zdenek Hodny, Eugenie Nepovimova
Summary: Rapamycin, the most extensively studied drug in anti-aging research, has limited physicochemical properties. This study utilized virtual high-throughput screening and fragment-based design to search for novel mTOR inhibiting scaffolds with suitable physicochemical parameters. Compound 3 demonstrated significant cytotoxic, senolytic, and senomorphic effects on normal and cancerous cells, making it a potential candidate for further investigation.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Parasitology
Sajad Rashidi, Reza Mansouri, Mohammad Ali-Hassanzadeh, Zahra Mojtahedi, Reza Shafiei, Amir Savardashtaki, Nasrin Hamidizadeh, Mohammadreza Karimazar, Paul Nguewa, Raul Manzano-Roman
Summary: The mTOR signaling pathway plays a crucial role in cell growth, metabolic regulation, and pathogen infections, connecting key host responses such as autophagy and immune responses. Understanding the complex regulatory mechanisms of mTOR may provide insights into developing novel therapeutic strategies against parasitic diseases.
PARASITOLOGY RESEARCH
(2021)
Article
Oncology
Vanitha N. Sivalingam, Ayse Latif, Sarah Kitson, Rhona McVey, Katherine G. Finegan, Kay Marshall, Michael P. Lisanti, Federica Sotgia, Ian J. Stratford, Emma J. Crosbie
BRITISH JOURNAL OF CANCER
(2020)
Article
Cell Biology
Bela Ozsvari, Federica Sotgia, Michael P. Lisanti
Article
Cell Biology
Camillo Sargiacomo, Federica Sotgia, Michael P. Lisanti
Article
Oncology
Bela Ozsvari, Luma G. Magalhaes, Joe Latimer, Jussi Kangasmetsa, Federica Sotgia, Michael P. Lisanti
FRONTIERS IN ONCOLOGY
(2020)
Article
Oncology
Rosa Sanchez-Alvarez, Ernestina Marianna De Francesco, Marco Fiorillo, Federica Sotgia, Michael P. Lisanti
FRONTIERS IN ONCOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Francesca De Santis, Giovanni Fuca, Dirk Schadendorf, Alberto Mantovani, Luca Magnani, Michael Lisanti, Stephen Pettitt, Matteo Bellone, Giannino Del Sal, Saverio Minucci, Alexander Eggermont, Paolo Bruzzi, Silvio Bicciato, Pierfranco Conte, Roberta Noberini, John Hiscott, Filippo De Braud, Michele Del Vecchio, Massimo Di Nicola
Summary: Experts at the Tenth Edition of the Annual Congress on Anticancer Innovative Therapy shared the latest knowledge and novel therapeutic approaches in fields such as immuno-oncology, epigenetics, cancer metabolism, cancer stem cells, tumor cell signaling, and the immune system. The conference also discussed possible mechanisms of resistance to these innovative therapies, particularly with respect to immune checkpoint blockers (ICB), providing a broad overview of future challenges and hopes for improving cancer treatment in the medium-short term.
CYTOKINE & GROWTH FACTOR REVIEWS
(2021)
Article
Multidisciplinary Sciences
Cristian Scatena, Giovanni Fanelli, Giuseppe Nicolo Fanelli, Michele Menicagli, Paolo Aretini, Valerio Ortenzi, Sara Piera Civitelli, Lorenzo Innocenti, Federica Sotgia, Michael P. Lisanti, Antonio Giuseppe Naccarato
Summary: Recent evidence indicates that loss of caveolin expression in the stromal compartment of human invasive breast carcinoma may be predictive of disease recurrence, metastasis, and poor prognosis. Additionally, a study on sCav-1 expression in breast cancer and axillary lymph nodes suggests that the loss of Cav-1 in lymph nodes may contribute to metastatic spread in breast cancer.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Marco Fiorillo, Cristian Scatena, Antonio Giuseppe Naccarato, Federica Sotgia, Michael P. Lisanti
Summary: This study identifies high ATP production by the mitochondrial ATP-synthase as a new therapeutic target for anticancer therapy, particularly for inhibiting tumor progression. ATP-high cancer cells exhibit aggressive phenotypes with increased proliferation, stemness, anchorage-independence, cell migration, invasion, and multi-drug resistance, along with high antioxidant capacity. ATP depletion through targeting ATP5F1C may serve as a promising strategy for preventing metastasis and avoiding treatment failure, making ATP5F1C a potential biomarker and molecular target for future drug development to prevent metastatic disease progression.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Immunology
Jacqueline S. Eacret, Elizabeth M. Parzych, Donna M. Gonzales, James M. Burns
Summary: The use of PfMSP8 as a carrier to optimize a PfMSP2-based subunit malaria vaccine showed promising results in terms of antibody production and T cell recognition. The choice of adjuvant impacted the specificity and functionality of induced antibodies.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Camillo Sargiacomo, Sophie Stonehouse, Zahra Moftakhar, Federica Sotgia, Michael P. Lisanti
Summary: MTDR can be used to target and eradicate cancer stem cells by selectively interfering with mitochondrial metabolism in breast cancer cells. It significantly inhibits tumor growth and metastasis with little to no toxicity observed in a preclinical animal model.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Filippo Di Pisa, Elisa Pesenti, Maria Bono, Andrea N. Mazzarello, Cinzia Bernardi, Michael P. Lisanti, Giovanni Renzone, Andrea Scaloni, Ermanno Ciccone, Franco Fais, Silvia Bruno, Paolo Scartezzini, Fabio Ghiotto
Summary: This study sheds light on the potential role of SH3BGRL3 in regulating myosin-cytoskeleton interaction and cell migration. It was found that SH3BGRL3 specifically interacts with Myo1c in a Ca2+-dependent manner, suggesting a potential regulatory mechanism for cytoskeleton dynamics involving SH3BGRL3 and Myo1c.
BMC MOLECULAR AND CELL BIOLOGY
(2021)
Review
Oncology
Marco Fiorillo, Bela Ozsvari, Federica Sotgia, Michael P. Lisanti
Summary: The study suggests that high mitochondrial ATP production is a new therapeutic target for cancer treatment, isolating metabolically fit cancer cells with enhanced stem-like properties and invasive abilities. By regulating mitochondrial ATP-synthase, prevention of metastasis in cancer cells is possible.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Matteo Brindisi, Luca Frattaruolo, Marco Fiorillo, Vincenza Dolce, Federica Sotgia, Michael P. Lisanti, Anna Rita Cappello
Summary: This study found that elevated cholesterol levels increase the aggressiveness of breast cancer cells and promote the release of pro-inflammatory factors. Furthermore, there is a close symbiotic relationship between breast cancer cells and the microenvironment. These findings highlight the potential of targeting the cholesterol-ERR alpha synergy for breast cancer treatment.
Article
Cell Biology
Nils Wellhausen, Ryan P. O'Connell, Stefanie Lesch, Nils W. Engel, Austin K. Rennels, Donna Gonzales, Friederike Herbst, Regina M. Young, K. Christopher Garcia, David Weiner, Carl H. June, Saar I. Gill
Summary: This study aims to develop a universal CAR T cell therapy targeting the pan-leukocyte marker CD45. By editing the epitope on CD45, healthy hematopoietic cells can be protected from CAR T cell toxicity while maintaining the essential functions of CD45. This therapy demonstrates efficacy against multiple blood cancers and shows good tolerability and effectiveness in experiments. Additionally, edited hematopoietic stem cells can engraft and differentiate in vivo.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Sundee Dees, Laura Pontiggia, Jean-Francois Jasmin, Federica Sotgia, Michael P. Lisanti, Isabelle Mercier