Review
Biochemistry & Molecular Biology
Julia Kallenbach, Golnaz Atri Roozbahani, Mehdi Heidari Horestani, Aria Baniahmad
Summary: This review analyzes the mechanisms of therapy-induced senescence (TIS) in PCa and finds that different molecular pathways are used by cancer cells for TIS. Understanding the complexity and underlying mechanisms of cellular senescence is critical for tumorigenesis.
CELL AND BIOSCIENCE
(2022)
Article
Multidisciplinary Sciences
Ximeng Liu, Xu Li, Shuang Wang, Qin Liu, Xianming Feng, Wenting Wang, Zhangduo Huang, Yongbo Huang, Jueheng Wu, Muyan Cai, Xiuyu Cai, Xiaonan Xu, Junchao Cai, Mengfeng Li
Summary: This study reveals the role of SMAD3 in oncogene-induced senescence and its conversion to malignant transformation. SMAD3, activated by high-level transforming growth factor B1 (TGF-B1) following oncogene Ras overactivation in lung epithelial cells, induces cellular senescence through the repression of cell cycle-promoting genes. Interestingly, SMAD3 also has an oncogenic effect and facilitates oncogene Ras-driven malignant transformation. Furthermore, the study identifies the potential tumor suppressor ATOH8 as a binding partner of SMAD3 and shows that its loss accelerates oncogene Ras-driven lung tumorigenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Conor Hanna, Victoria L. Dunne, Steven M. Walker, Karl T. Butterworth, Nuala McCabe, David J. J. Waugh, Richard D. Kennedy, Kevin M. Prise
Summary: Prostate cancer is the most frequently diagnosed cancer in men, with the role of the PTEN gene being complex but important in its treatment. Studies suggest that in the absence of PTEN, combined treatment using radiotherapy and the ATM inhibitor KU-60019 has a greater therapeutic effect.
Article
Oncology
Shawn M. Davidson, Daniel R. Schmidt, Julia E. Heyman, James P. O. 'Brien, Amy C. Liu, William J. Israelsen, Talya L. Dayton, Raghav Sehgal, Roderick T. Bronson, Elizaveta Freinkman, Howard H. Mak, Giuseppe Nicolo Fanelli, Scott Malstrom, Gary Bellinger, Arkaitz Carracedo, Pier Paolo Pandolfi, Kevin D. Courtney, Abhishek Jha, Ronald A. DePinho, James W. Horner, Craig J. Thomas, Lewis C. Cantley, Massimo Loda, Matthew G. Vander Heiden
Summary: This study reveals the impact of differential expression of pyruvate kinase isoforms on cancer initiation and progression. The M2 splice isoform of pyruvate kinase (PKM2) supports cancer cell proliferation and survival in prostate cancer, while the M1 isoform (PKM1) has a suppressive effect on tumor development. Alterations in nucleotide levels are observed in tumors with high PKM1 expression, leading to DNA replication stress and senescence which inhibits tumor progression. A small molecule pyruvate kinase activator that mimics the high activity PKM1-like state can suppress the progression of established prostate tumors.
Article
Oncology
Zongliang Lu, Wei Song, Yaowen Zhang, Changpeng Wu, Mingxing Zhu, He Wang, Na Li, Yong Zhou, Hongxia Xu
Summary: Combining Platycodin D with sorafenib can enhance sorafenib-induced apoptosis and cell cycle arrest in prostate cancer cells, particularly in Akt-positive and PTEN-negative cells, indicating a promising approach for the treatment of castration-resistant and PTEN-deficient prostate cancer through potent anti-cancer effects via FOXO3a.
FRONTIERS IN ONCOLOGY
(2021)
Article
Physics, Fluids & Plasmas
Chandrashekar Kuyyamudi, Shakti N. Menon, Sitabhra Sinha
Summary: We demonstrate that heterogeneity in cell shapes and sizes, in the context of contact-mediated interactions, can result in qualitatively different collective behavior in tissues. When lateral inhibition is implemented through intercellular coupling, these disorder-driven transitions can significantly alter the ultimate differentiation pattern of cells by modifying their fate choice through changes in neighborhood geometry. Furthermore, when contact-induced signals affect inherent cellular oscillations, disorder can lead to the emergence of partially-ordered dynamical states that are functionally relevant.
Article
Chemistry, Multidisciplinary
Min Ju Kim, Hyosuk Kim, Xueliang Gao, Ju Hee Ryu, Yoosoo Yang, Ick Chan Kwon, Thomas M. Roberts, Sun Hwa Kim
Summary: A multi-targeting siRNA delivery system was proposed for PI3K-targeted anticancer therapy, effectively inhibiting the PI3K signaling pathway in PTEN-deficient cancer cells, leading to delays in cell proliferation and migration.
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
(2021)
Article
Oncology
Xueliang Gao, Yubao Wang, Caroline F. Ribeiro, Cherubin Manokaran, Hyeyoun Chang, Thanh Von, Silvia Rodrigues, Onur Cizmecioglu, Shidong Jia, Manav Korpal, Joshua M. Korn, Zhigang Wang, Fabienne Schmit, Lan Jiang, Raymond Pagliarini, Yi Yang, Isha Sethi, Sabina Signoretti, Guo-Cheng Yuan, Massimo Loda, Jean J. Zhao, Thomas M. Roberts
Summary: Research findings suggest that blocking p110 beta can slow down the progression of castration-resistant prostate cancer and reduce tumor growth. Combining p110 beta with other inhibitors shows potential for treating CRPC.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Debora C. Bastos, Caroline F. Ribeiro, Thomas Ahearn, Jessica Nascimento, Hubert Pakula, John Clohessy, Lorelei Mucci, Thomas Roberts, Silvio M. Zanata, Giorgia Zadra, Massimo Loda
Summary: The loss of PTEN tumor suppressor gene in murine prostate results in stromal proliferation and reactive microinvasion. Genetic ablation of FASN reduces prostate weight and volume, abolishing stromal reaction and cell proliferation associated with PTEN knockout. Inhibition of FASN significantly decreases cellular motility and invasion potential in prostate cancer, suggesting a potential therapeutic target for aggressive prostate cancer driven by PTEN loss.
JOURNAL OF PATHOLOGY
(2021)
Article
Oncology
Marco A. De Velasco, Yurie Kura, Naomi Ando, Noriko Sako, Eri Banno, Kazutoshi Fujita, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuko Sakai, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura
Summary: The study demonstrates potent antitumor activity of apalutamide in early-stage and late-stage castration-naive prostate cancer models, but limited efficacy in castration-resistant prostate cancer. Additionally, the therapeutic potential of combined AR/AKT inhibition was shown to be more promising in vitro than in vivo, possibly due to upregulation of STAT3 and PIM-1.
Article
Biology
Alexandre A. Germanos, Sonali Arora, Ye Zheng, Erica T. Goddard, Ilsa M. Coleman, Anson T. Ku, Scott Wilkinson, Hanbing Song, Nicholas J. Brady, Robert A. Amezquita, Michael Zager, Annalysa Long, Yu Chi Yang, Jason H. Bielas, Raphael Gottardo, David S. Rickman, Franklin W. Huang, Cyrus M. Ghajar, Peter S. Nelson, Adam G. Sowalsky, Manu Setty, Andrew C. Hsieh
Summary: In this study, we found that the expansion of castration-resistant intermediate luminal cells is associated with treatment resistance and poor prognosis in prostate cancer. The transformed epithelial cells and associated fibroblasts create a microenvironment that promotes pro-tumorigenic immune infiltration, which is influenced by androgen levels. Androgen-independent prostate cancer leads to significant diversification of intermediate luminal cell populations with varying androgen signaling activities, which are inversely correlated with proliferation and mRNA translation. The findings suggest that targeting translation inhibition could potentially lead to epithelial cell death, loss of pro-tumorigenic signaling, and decreased tumor heterogeneity.
Article
Oncology
Ilaria Guccini, Ajinkya Revandkar, Mariantonietta D'Ambrosio, Manuel Colucci, Emiliano Pasquini, Simone Mosole, Martina Troiani, Daniela Brina, Raheleh Sheibani-Tezerji, Angela Rita Elia, Andrea Rinaldi, Nicolo Pernigoni, Jan Hendrik Ruschoff, Susanne Dettwiler, Angelo M. De Marzo, Emmanuel S. Antonarakis, Costanza Borrelli, Andreas E. Moor, Ramon Garcia-Escudero, Abdullah Alajati, Giuseppe Attanasio, Marco Losa, Holger Moch, Peter Wild, Gerda Egger, Andrea Alimonti
Summary: Metastasis in prostate cancer is influenced by senescence with TIMP1 acting as a molecular switch. Elimination of senescent cells can impair tumor metastasis.
Article
Geriatrics & Gerontology
Seul Gi Kim, Jin Young Sung, Jae-Ryong Kim, Hyoung Chul Choi
Summary: Cellular senescence is influenced by various intracellular and extracellular stimuli, with PTEN and mTORC2 playing key roles in vascular smooth muscle cells. The mTORC2-Akt signaling pathway could be a potential target for preventing age-related diseases.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Lei Fang, Dongmei Li, JuanJuan Yin, Hong Pan, Huihui Ye, Joel Bowman, Brian Capaldo, Kathleen Kelly
Summary: ERG translocations play a key role in the initiation of prostate neoplasia. However, the mechanisms of oncogenic inception have not been fully understood. In this study, a genetically engineered mouse model was used to investigate the effects of combined TMPRSS2-driven ERG and Kras(G12D) on prostate adenocarcinomas. It was found that the presence of TMPRSS2-ERG, along with Kras(G12D), promoted tumorigenesis and metastasis of primary luminal cells. Additionally, TMPRSS2-ERG suppressed oncogene-induced senescence, leading to the accumulation of additional gene mutations. This study reveals a previously unknown function of ERG expression in priming preneoplastic cells for oncogenic mutations.
CANCER GENE THERAPY
(2022)
Article
Physics, Fluids & Plasmas
Chandrashekar Kuyyamudi, Shakti N. Menon, Sitabhra Sinha
Summary: Cells in developing embryos differentiate reliably despite fluctuations in morphogen concentrations and molecular processes, by utilizing cell-cell interactions and the asymmetry in gene response to global morphogen signals. This bimodal response ensures consistent developmental outcomes and reduces uncertainty in boundary locations between distinct fates.
Review
Oncology
Sara Napoli, Nicolas Munz, Francesca Guidetti, Francesco Bertoni
Summary: This review provides an overview of the mechanisms by which enhancer RNAs (eRNAs) regulate gene expression, with a focus on the latest examples of dysregulated eRNAs in cancer and their involvement in the immune escape of tumor cells. eRNAs play an important role in transcriptional regulation during cellular differentiation and are induced by specific stimuli to activate target gene promoters. Dysregulation of eRNAs is common in cancer and they interact with chromatin modifiers, transcription factors, and splicing machinery. Activation of enhancers and eRNA transcription also play a significant role in inflammatory response and the interaction between cancer and immune cells.
Article
Medicine, General & Internal
Samantha Epistolio, Giulia Ramelli, Margaret Ottaviano, Emanuele Crupi, Laura Marandino, Maira Biggiogero, Pier Andrea Maida, Lorenzo Ruinelli, Ursula Vogl, Dylan Mangan, Mariarosa Pascale, Marco Cantu, Alessandro Ceschi, Enos Bernasconi, Luca Mazzucchelli, Carlo Catapano, Andrea Alimonti, Christian Garzoni, Silke Gillessen Sommer, Federico Mattia Stefanini, Alessandra Franzetti-Pellanda, Milo Frattini, Ricardo Pereira Mestre
Summary: The study found that the HSD3B1 gene polymorphism status may influence the severity of SARS-CoV-2 infection in COVID-19 patients. The HSD3B1 variants played a clinical role in specific subgroups, such as affecting ICU admission and mortality rates.
FRONTIERS IN MEDICINE
(2022)
Editorial Material
Urology & Nephrology
Editorial Eugene Shenderov, Emmanuel S. Antonarakis
Article
Multidisciplinary Sciences
Miriam Saponaro, Sina Flottmann, Markus Eckstein, Oliver Hommerding, Niklas Kluemper, Dillon Corvino, Sana Hosni, Anja Schmidt, Nicolas Moenig, Doris Schmidt, Joerg Ellinger, Marieta Toma, Glen Kristiansen, Tobias Bald, Andrea Alimonti, Manuel Ritter, Michael Hoelzel, Abdullah Alajati
Summary: The poor prognosis of advanced urothelial carcinoma (UC) and the need for improved treatment have led researchers to investigate the role of CUB domain containing protein 1 (CDCP1) in UC. They found that CDCP1 is highly expressed in advanced UC and its overexpression is associated with shorter overall survival. Experiments with organoids and cell lines demonstrated that CDCP1 plays an oncogenic role by activating the MAPK/ERK pathway and promoting proliferation and migration. Targeting CDCP1 could be a rational therapeutic strategy for advanced UC.
SCIENTIFIC REPORTS
(2023)
Article
Physiology
Federica Mangione, Rocco D'Antuono, Nicolas Tapon
Summary: Tissues consist of diverse cell populations and it is challenging to dissect the contributions of different cell types. This study presents a method using near infrared femtosecond laser pulses for precise cell ablation without harming neighboring tissues. The technique allows monitoring of cellular behavior and morphological responses to cell loss with high resolution.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Medicine, General & Internal
Francesca Guidetti, Alberto J. Arribas, Giulio Sartori, Filippo Spriano, Laura Barnabei, Chiara Tarantelli, Reinhard Von Roemeling, Elizabeth Martinez, Emanuele Zucca, Francesco Bertoni
Summary: Inhibitors of PI3K and BTK have limited success in inducing complete responses in indolent B cell lymphomas, suggesting the need for combination therapies. The IRAK4 inhibitor emavusertib shows effectiveness as a single agent and in combination with targeted agents, including overcoming resistance to BTK and PI3K inhibitors. Emavusertib exerts its activity through inhibition of NF-kappa B signaling and induction of apoptosis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Nicolo Bancaro, Bianca Cali, Martina Troiani, Angela Rita Elia, Rydell Alvarez Arzola, Giuseppe Attanasio, Ping Lai, Mateus Crespo, Bora Gurel, Rita Pereira, Christina Guo, Simone Mosole, Daniela Brina, Mariantonietta D'Ambrosio, Emiliano Pasquini, Clarissa Spataro, Elena Zagato, Andrea Rinaldi, Mattia Pedotti, Simona Di Lascio, Francesco Meani, Monica Montopoli, Matteo Ferrari, Andrea Gallina, Luca Varani, Ricardo Pereira Mestre, Marco Bolis, Silke Gillessen Sommer, Johann de Bono, Arianna Calcinotto, Andrea Alimonti
Summary: Tumor cells promote the recruitment of immunosuppressive neutrophils, a subset of myeloid cells driving immune suppression, tumor proliferation, and treatment resistance. We have identified a subset of neutrophils that have upregulated expression of cellular senescence markers and persist in the tumor microenvironment. These senescent-like neutrophils express TREM2 and are more immunosuppressive and tumor-promoting than canonical immunosuppressive neutrophils.
Article
Cell Biology
Rydell Alvarez-Arzola, Nicolo Bancaro, Ping Lai, Giuseppe Attanasio, Laura Pellegrini, Martina Troiani, Manuel Colucci, Simone Mosole, Emiliano Pasquini, Andrea Alimonti, Circe Mesa
Summary: Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer, but some patients develop castration-resistant prostate cancer (CRPC). Activating ex vivo-activated macrophages as immunotherapy shows potential for treating CRPC by inhibiting tumor growth and reducing angiogenesis and proliferation.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Clinical Neurology
Maurizio Fava, Stephen M. M. Stahl, Sara De Martin, Andrea Mattarei, Ezio Bettini, Stefano Comai, Andrea Alimonti, Francesco Bifari, Luca Pani, Franco Folli, Clotilde Guidetti, Alberto Furlan, Jacopo Sgrignani, Patrizia Locatelli, Andrea Cavalli, Cedric O'Gorman, Sergio Traversa, Charles E. E. Inturrisi, Marco Pappagallo, Paolo L. L. Manfredi
Summary: This review article discusses recent studies on the development of esmethadone as a potential new drug. Esmethadone is a member of the pharmacological class of uncompetitive NMDAR antagonists and has shown efficacy for MDD and other diseases. The article also compares esmethadone with other NMDAR antagonists. It presents data from in silico, in vitro, in vivo, and clinical studies that contribute to our understanding of the role of these receptors in neural plasticity in health and disease. The efficacy of NMDAR antagonists as rapid antidepressants has implications for the neurobiology of MDD and other neuropsychiatric disorders.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Correction
Multidisciplinary Sciences
Miriam Saponaro, Sina Flottmann, Markus Eckstein, Oliver Hommerding, Niklas Kluemper, Dillon Corvino, Sana Hosni, Anja Schmidt, Nicolas Moenig, Doris Schmidt, Joerg Ellinger, Marieta Toma, Glen Kristiansen, Tobias Bald, Andrea Alimonti, Manuel Ritter, Michael Hoelzel, Abdullah Alajati
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Jack Major, Stefania Crotta, Katja Finsterbusch, Probir Chakravarty, Kathleen Shah, Bruno Frederico, Rocco D'Antuono, Mary Green, Lucy Meader, Alejandro Suarez-Bonnet, Simon Priestnall, Brigitta Stockinger, Andreas Wack
Summary: Disruption of the lung endothelial-epithelial cell barrier following respiratory virus infection compromises vital gas exchange function and exacerbates tissue damage. The environmental sensor aryl hydrocarbon receptor (AHR) plays a protective role against influenza-induced lung vascular leakage. Loss of AHR in endothelial cells worsens lung damage, promotes cell and fluid accumulation, compromises barrier protection, and increases susceptibility to secondary bacterial infections. AHR engagement in endothelial cells prevents dysplastic and apoptotic responses in airway epithelial cells. Additionally, the protective AHR signaling is dampened by the infection itself, and maintenance of AHR function requires a diet enriched in naturally occurring AHR ligands.
Article
Urology & Nephrology
Nicolo Pernigoni, Christina Guo, Lewis Gallagher, Wei Yuan, Manuel Colucci, Martina Troiani, Lei Liu, Luisa Maraccani, Ilaria Guccini, Denis Migliorini, Johann de Bono, Andrea Alimonti
Summary: The microbiota, a complex and dynamic population of microorganisms in the human body, has been found to play a role in the development and progression of prostate cancer. Specific microbial species in the urine and gut have been associated with an increased risk of prostate cancer, but the causal mechanisms are still not well understood. Mechanistic evidence suggests that bacterial generation of genotoxins and production of androgenic steroids by the gut microbiota may contribute to prostate carcinogenesis and therapeutic resistance. These findings open up potential avenues for the diagnosis and treatment of prostate cancer by profiling and modulating the host microbiota.
NATURE REVIEWS UROLOGY
(2023)
Article
Multidisciplinary Sciences
Ilaria Guccini, Guanghui Tang, Trang Thuy To, Laura Di Rito, Solange Le Blanc, Oliver Strobel, Mariantonietta D'Ambrosio, Emiliano Pasquini, Marco Bolis, Pamuditha Silva, Hasan Ali Kabakci, Svenja Godbersen, Andrea Alimonti, Gerald Schwank, Markus Stoffel
Summary: The rate-limiting enzyme of fructose metabolism, KHK, is found to be a driver of pancreatic cancer (PDAC) development. Fructose triggers the activation of KHK and induces the expression of fructolytic genes in PDAC. Genetic inactivation of KhkC enhances the survival of KPC-driven PDAC and reduces the viability and growth of KPC cells, likely through impairing KRAS-MAPK pathway and mTORC signaling. These findings suggest that inhibiting KHK could be a promising therapeutic strategy for pancreatic cancer.
Article
Oncology
Daniela Brina, Adele Ponzoni, Martina Troiani, Bianca Cali, Emiliano Pasquini, Giuseppe Attanasio, Simone Mosole, Michela Mirenda, Mariantonietta D'Ambrosio, Manuel Colucci, Ilaria Guccini, Ajinkya Revandkar, Abdullah Alajati, Toma Tebaldi, Deborah Donzel, Fabio Lauria, Nahjme Parhizgari, Aurora Valdata, Martino Maddalena, Arianna Calcinotto, Marco Bolis, Andrea Rinaldi, Simon Barry, Jan Hendrik Rueschoff, Marianna Sabbadin, Semini Sumanasuriya, Mateus Crespo, Adam Sharp, Wei Yuan, Mathew Grinu, Alexandra Boyle, Cynthia Miller, Lloyd Trotman, Nicolas Delaleu, Matteo Fassan, Holger Moch, Gabriella Viero, Johann de Bono, Andrea Alimonti
Summary: In prostate cancer, the secretome is rewired at the translational level to recruit MDSCs, with Hgf, Spp1, and Bgn identified as key regulators. By inhibiting the MNK/eIF4E and AKT pathways, this study provides a therapeutic strategy that combines translation inhibition with immunotherapy to restore immune surveillance in prostate cancer.
Review
Oncology
Carmen de Ramon Ortiz, Sisi Wang, Anastasios Stathis, Francesco Bertoni, Thorsten Zenz, Urban Novak, Federico Simonetta
Summary: About one third of DLBCL patients experience relapsing/refractory disease after first line chemo-immunotherapy. CAR T cell therapy targeting CD19 is a game changer in the treatment of R/R DLBCL and shows promising results. However, the timing and sequencing of different anti-CD19-targeting therapies and their impact on subsequent CAR T cell treatment is still unclear.
HEMATOLOGICAL ONCOLOGY
(2023)
