Review
Biochemistry & Molecular Biology
Irene Zamora, Michael R. Freeman, Ignacio J. Encio, Mirja Rotinen
Summary: Neuroendocrine prostate cancer is a highly aggressive subtype of prostate cancer that can evade traditional therapies. Recent molecular research has identified factors driving its development and potential therapeutic targets. Current investigations into treatments show promise in improving patient prognosis for this lethal disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pathology
Eman Abdulfatah, Samson W. Fine, Tamara L. Lotan, Rohit Mehra
Summary: This review provides an overview of the pathological and immunohistochemical features, emerging biomarkers, and molecular features of neuroendocrine tumors of the prostate. The classification of these tumors is challenging, with some arising in castration-resistant prostate cancer and others being de novo cases.
Review
Oncology
Lina Merkens, Verena Sailer, Davor Lessel, Ella Janzen, Sarah Greimeier, Jutta Kirfel, Sven Perner, Klaus Pantel, Stefan Werner, Gunhild von Amsberg
Summary: Prostate cancer is a hormone-driven disease and targeted therapies against androgen receptor (AR) signaling have been widely used. However, some patients eventually develop castration-resistant disease. Aggressive variant prostate cancer (AVPC) with neuroendocrine differentiation has emerged and its growth is independent of the AR pathway. Understanding the molecular mechanisms contributing to transdifferentiation is crucial for improving diagnosis and treatment strategies.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Che-Yuan Hu, Kuan-Yu Wu, Tsung-Yen Lin, Chien-Chin Chen
Summary: This review provides an overview of the interaction between long non-coding RNAs and microRNAs in prostate cancer, and discusses their influence on castration resistance or neuroendocrine differentiation. Additionally, it explores the mechanisms of lncRNA-miRNA interaction in androgen receptor-independent prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Neha Singh, Varune R. Ramnarine, Jin H. Song, Ritu Pandey, Sathish K. R. Padi, Mannan Nouri, Virginie Olive, Maxim Kobelev, Koichi Okumura, David McCarthy, Michelle M. Hanna, Piali Mukherjee, Belinda Sun, Benjamin R. Lee, J. Brandon Parker, Debabrata Chakravarti, Noel A. Warfel, Muhan Zhou, Jeremiah J. Bearss, Ewan A. Gibb, Mohammed Alshalalfa, R. Jefferey Karnes, Eric J. Small, Rahul Aggarwal, Felix Feng, Yuzhuo Wang, Ralph Buttyan, Amina Zoubeidi, Mark Rubin, Martin Gleave, Frank J. Slack, Elai Davicioni, Himisha Beltran, Colin Collins, Andrew S. Kraft
Summary: The long noncoding RNA H19 plays a critical role in neuroendocrine prostate cancer by promoting cellular plasticity through epigenetic reprogramming, influencing lineage plasticity and treatment resistance in prostate cancer cells.
NATURE COMMUNICATIONS
(2021)
Review
Endocrinology & Metabolism
William K. Storck, Allison M. May, Thomas C. Westbrook, Zhi Duan, Colm Morrissey, Joel A. Yates, Joshi J. Alumkal
Summary: The androgen receptor (AR) signaling pathway plays a critical role in the growth and differentiation of prostate cancer cells. Androgen deprivation therapy is the main treatment for metastatic prostate cancer, but resistance to AR signaling inhibitors is common. Lineage plasticity, specifically the switch to an alternate differentiation program, is a recently identified resistance mechanism. This review discusses the role of AR pathway loss and activation of a neuronal differentiation program in lineage plasticity, and explores new epigenetic therapeutic strategies to reverse this process.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pathology
Eman Abdulfatah, Samson W. Fine, Tamara L. Lotan, Rohit Mehra
Summary: Neuroendocrine tumors of the prostate are rare and classification based on morphological and immunohistochemical features may not always be sufficient. This review focuses on the important pathological and immunohistochemical features, emerging biomarkers, and molecular features of these tumors.
Article
Oncology
Anthony Turpin, Carine Delliaux, Pauline Parent, Hortense Chevalier, Carmen Escudero-Iriarte, Franck Bonardi, Nathalie Vanpouille, Anne Flourens, Jessica Querol, Aurelien Carnot, Xavier Leroy, Nicolas Herranz, Tristan Lanel, Arnauld Villers, Jonathan Olivier, Helene Touzet, Yvan de Launoit, Tian V. Tian, Martine Duterque-Coquillaud
Summary: Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer associated with resistance to androgen-deprivation therapies. This study reveals that the actin-bundling protein Fascin-1 (FSCN1) is upregulated during NEPC differentiation and is repressed by the androgen receptor (AR), contributing to NEPC aggressiveness. These findings suggest that targeting FSCN1 may be a potential therapeutic strategy for NEPC patients.
BRITISH JOURNAL OF CANCER
(2023)
Article
Mathematics, Applied
Leo Turner, Andrew Burbanks, Marianna Cerasuolo
Summary: This paper explores the role of neuroendocrine transdifferentiation in human prostate cancer cell dynamics using a nonlinear mathematical model. It provides sufficient conditions for the biological relevance of the model's solutions and the existence of its equilibria. The global asymptotic stability of the tumour-free equilibrium is proven, and parameters responsible for bifurcations are identified through sensitivity and bifurcation analyses.
NONLINEAR ANALYSIS-MODELLING AND CONTROL
(2021)
Article
Biochemistry & Molecular Biology
Liancheng Fan, Yiming Gong, Yuman He, Wei-Qiang Gao, Xuesen Dong, Baijun Dong, Helen He Zhu, Wei Xue
Summary: The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been increasing due to the usage of second-generation androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with poor prognosis in PCa patients. Upregulation of TRIM59 is strongly correlated with ARPI treatment mediated NED and shorter patient survival in PCas. TRIM59, negatively regulated by AR, acts as a key driver for NED in PCas and provides a novel prognostic marker for PCas.
Review
Medical Laboratory Technology
Ke Lu, Muyuan Yu, Yongchang Chen
Summary: Research has shown that non-coding RNAs may play a significant role in the progression of prostate cancer, participating in the regulatory network of AR signaling and helping identify new molecular mechanisms to promote the disease.
CLINICA CHIMICA ACTA
(2021)
Article
Oncology
Charly Blanc, Anissa Moktefi, Ariane Jolly, Pierre de la Grange, Denise Gay, Nathalie Nicolaiew, Fannie Semprez, Pascale Maille, Pascale Soyeux, Virginie Firlej, Francis Vacherot, Damien Destouches, Mohamed Amiche, Stephane Terry, Alexandre de la Taille, Arturo Londono-Vallejo, Yves Allory, Jean Delbe, Yamina Hamma-Kourbali
Summary: This study identifies Neuropilin-1 (NRP1) as a key component of neuroendocrine prostate cancer (NEPC) and shows that NRP1 is activated during androgen deprivation therapies (ADT), promoting cell survival through the PKC pathway and leading to the development of castration resistance. Inhibition of NRP1 or PKC can suppress neuroendocrine differentiation, prevent tumor evolution towards castration resistance, and enhance the efficacy of docetaxel-based chemotherapy. These findings suggest that the NRP1/PKC axis could be a promising therapeutic target for preventing NEPC and that NRP1 may serve as an early transitional biomarker.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Ming Han, Feii Li, Yehan Zhang, Pengfei Dai, Juan He, Yunguang Li, Yiqin Zhu, Junke Zheng, Hai Huang, Fan Bai, Dong Gao
Summary: Prostate cancer adeno-to-neuroendocrine lineage transition is driven by FOXA2 and is regulated by the KIT pathway. Inhibiting the KIT pathway can suppress the growth of neuroendocrine prostate cancer. This study provides insights into the molecular mechanisms behind therapeutic resistance in prostate cancer.
Article
Immunology
Hongda Pan, Jingxin Pan, Jianghong Wu
Summary: This study developed a CAF-derived long non-coding RNA (CAF DL) signature for predicting clinical outcomes in colorectal cancer (CRC). The signature showed significant predictive power in multiple cancers and could serve as a useful tool for risk stratification and understanding the underlying mechanisms of CAFs in cancer immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Xiaomei Ma, Baoshun Yang, Yuan Yang, Guozhi Wu, Xiaoli Ma, Xiao Yu, Yingwen Li, Yuping Wang, Qinghong Guo
Summary: This study analyzed the role of N-7-methylguanosine (m7G) in colon cancer development and found that m7G-RNAs are associated with the prognosis and immune status of colon adenocarcinoma (COAD). A prognostic signature was developed and shown to reliably predict the prognosis of COAD. Additionally, the risk score was associated with immune cell infiltration.
FRONTIERS IN GENETICS
(2022)
Article
Dermatology
M. Scatolini, A. Patel, E. Grosso, M. Mello-Grand, P. Ostano, R. Coppo, M. Vitiello, T. Venesio, A. Zaccagna, A. Pisacane, I Sarotto, D. Taverna, L. Poliseno, D. Bergamaschi, G. Chiorino
Summary: The study identified a significant association between metastases, BRAF mutation, and low GJB5 expression in melanoma, suggesting a potential prognostic role for GJB5 in cutaneous melanoma.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Oncology
Simone Camelliti, Valentino Le Noci, Francesca Bianchi, Chiara Storti, Francesca Arnaboldi, Alessandra Cataldo, Serena Indino, Elena Jachetti, Mariangela Figini, Mario Paolo Colombo, Andrea Balsari, Nicoletta Gagliano, Elda Tagliabue, Lucia Sfondrini, Michele Sommariva
Summary: TLR9-stimulated macrophages interacting with the Fc domain of anti-PD-1 antibody acquire an immunoregulatory phenotype, leading to dampening of CpG-ODN antitumor effect. This may represent another possible mechanism of anti-PD-1 antibody therapy resistance.
Article
Biology
Claudio Tripodo, Barbara Bassani, Elena Jachetti, Valeria Cancila, Claudia Chiodoni, Paola Portararo, Laura Botti, Cesare Vaenti, Milena Perrone, Maurilio Ponzoni, Patrizia Comoli, Mara Lecchi, Paolo Verderio, Antonio Curti, Mario P. Colombo, Sabina Sangaletti
Summary: Neutrophil extracellular traps (NETs) are web-like chromatin structures composed of dsDNA and histones, decorated with antimicrobial proteins. Their interaction with dendritic cells (DCs) allows DC activation and maturation towards presentation of NET-associated antigens. NETs preserve the proteins localized onto the DNA threads for proper enzymatic activity and conformational status, including immunogenic epitopes. A NET/DC vaccine loaded with mutant NPMc+ NET effectively reduces myeloproliferation in transgenic mice and induces an anti-NPMc immune response.
Article
Cell Biology
Eirini Chrysanthou, Emir Sehovic, Paola Ostano, Giovanna Chiorino
Summary: Female melanoma patients have a lower incidence and better prognosis compared to males. Through statistical analysis of melanoma gene expression datasets, this study reveals sex and stage differences in gene expression. Specifically, females have lower gene expression variability in normal skin, nevi, and early-stage melanomas, while males have lower variability in stage III melanomas. Gene expression differences between sexes are most notable in non-melanoma and early-stage melanoma samples.
Article
Oncology
Silvia Marconi, Michela Croce, Giovanna Chiorino, Giovanni Rossi, Francesca Guana, Aldo Profumo, Paola Ostano, Angela Alama, Luca Longo, Giuseppa De Luca, Mariella Dono, Maria Giovanna Dal Bello, Marco Ponassi, Camillo Rosano, Paolo Romano, Zita Cavalieri, Massimiliano Grassi, Marco Tagliamento, Lodovica Zullo, Consuelo Venturi, Chiara Dellepiane, Luca Mastracci, Elisa Bennicelli, Paolo Pronzato, Carlo Genova, Simona Coco
Summary: This study performed in-depth analysis of circulating markers in early-stage non-small cell lung cancer (NSCLC) to identify a prognostic score for cancer recurrence prediction. The study found that the overexpression of Exo-miR-130a-3p and the reduction of FpA (2-16) were associated with cancer relapse, and high-risk patients had shorter disease-free survival. The overexpression of miR-130a-3p may lead to dysregulation of angiogenesis and coagulation pathways.
Article
Oncology
Sara De Martino, Egidio Iorio, Chiara Cencioni, Aurora Aiello, Francesco Spallotta, Mattea Chirico, Maria Elena Pisanu, Claudio Grassi, Alfredo Pontecorvi, Carlo Gaetano, Simona Nanni, Antonella Farsetti
Summary: Despite advances in cancer therapies, treatment-resistant relapse is still a challenge. Acquired resistance is a major factor leading to relapse, as seen in aggressive forms of prostate cancer. The study demonstrates the role of CHKA in lipid metabolism, specifically targeted by the long non-coding RNA MALAT1, providing insights into potential therapeutic options for metabolic rewiring in cancer treatment.
Article
Biochemistry & Molecular Biology
Marco Rinaudo, Francesca Natale, Francesco La Greca, Matteo Spinelli, Antonella Farsetti, Fabiola Paciello, Salvatore Fusco, Claudio Grassi
Summary: This study found that male mice are more susceptible to memory loss induced by retroactive interference than females. Estrogen signaling involving estrogen receptor alpha activation in the dorsal hippocampus mediates the resistance of female mice to retroactive interference. Female mice showed higher phosphorylation levels of ERK1/2 in the hippocampus following retroactive interference. Inhibition of ERK1/2 made female mice more prone to retroactive interference.
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
Immunology
Diego Signorelli, Patrizia Ghidotti, Claudia Proto, Marta Brambilla, Alessandro De Toma, Roberto Ferrara, Giulia Galli, Monica Ganzinelli, Giuseppe Lorusso, Arsela Prelaj, Mario Occhipinti, Giuseppe Viscardi, Valentina Capizzuto, Francesca Pontis, Ilaria Petraroia, Anna Maria Ferretti, Mario Paolo Colombo, Valter Torri, Gabriella Sozzi, Marina Chiara Garassino, Elena Jachetti, Orazio Fortunato
Summary: This study evaluated circulating EVs as potential biomarkers for ICI in NSCLC patients with low PD-L1. The results showed that higher levels of tetraspanins in R-EVs were associated with better treatment response and improved survival.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Chiara Arrigoni, Paola Ostano, Simone Bersini, Martina Crippa, Maria Vittoria Colombo, Mara Gilardi, Luigi Zagra, Maurizia Mello-Grand, Ilaria Gregnanin, Carmen Ghilardi, Maria Rosa Bani, Christian Candrian, Giovanna Chiorino, Matteo Moretti
Summary: Different tissues have different endothelial features. This study explores the implications of this heterogeneity in pathological responses, specifically in osteoarthritis (OA) and sarcopenia. The results show that inflammation affects bone and muscle endothelial cells differently, with increased angiogenesis in subchondral bone and impaired angiogenesis in muscle, possibly linking OA and sarcopenia.
COMMUNICATIONS BIOLOGY
(2023)
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)
Review
Pharmacology & Pharmacy
Roberta Sulsenti, Elena Jachetti
Summary: Tumor development, progression, and resistance to therapies are influenced by the interactions between tumor cells and the surrounding microenvironment, comprising fibroblasts, immune cells, and extracellular matrix proteins. In this context, mast cells (MCs) have recently emerged as important players. The role of MCs in promoting or inhibiting cancer growth is still controversial, and targeting MCs for cancer immunotherapy has become a potential strategy.
Article
Pharmacology & Pharmacy
Anna Luganini, Giulia Sibille, Marta Pavan, Maurizia Mello Grand, Stefano Sainas, Donatella Boschi, Marco L. Lolli, Giovanna Chiorino, Giorgio Gribaudo
Summary: Human respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections with no effective drugs available. This study characterized the molecular mechanisms of the anti-RSV activity of MEDS433, a new inhibitor that targets human dihydroorotate dehydrogenase (hDHODH). MEDS433 showed potent antiviral activity against RSV-A and RSV-B by suppressing viral genome synthesis and inducing the expression of antiviral proteins encoded by Interferon-Stimulated Genes (ISGs). Furthermore, MEDS433 effectively inhibited RSV-A replication in a primary human small airway epithelial cell model. These findings provide new insights for the development of MEDS433 as a promising candidate for RSV treatment.
ANTIVIRAL RESEARCH
(2023)
Meeting Abstract
Oncology
Roberto Ferrara, Giuseppe Lo Russo, Chiara Maura Ciniselli, Annamaria Piva, Barbara Bassani, Elena Jachetti, Giuseppina Calareso, Valeria Duroni, Settimio Di Gregorio, Claudia Proto, Arsela Prelaj, Alessandro De Toma, Mario Occhipinti, Marta Brambilla, Sara Manglaviti, Laura Mazzeo, Arturo Rinaldi, Teresa Beninato, Monica Ganzinelli, Filippo De Braud, Marina Chiara Garassino, Paolo Verderio, Mario Paolo Colombo, Sabina Sangaletti
Meeting Abstract
Oncology
D. Signorelli, O. Fortunato, F. Pontis, V. Capizzuto, R. Ferri, M. Brambilla, R. Ferrara, C. Proto, G. Lo Russo, A. Prelaj, G. Galli, A. De Toma, G. Viscardi, R. Lobefaro, F. Nichetti, M. Ganzinelli, N. Zilembo, M. Colombo, G. Sozzi, M. C. Garassino, E. Jachetti
JOURNAL OF THORACIC ONCOLOGY
(2021)