Review
Pharmacology & Pharmacy
Delphine Quatannens, Yannick Verhoeven, Peter Van Dam, Filip Lardon, Hans Prenen, Geert Roeyen, Marc Peeters, Evelien L. J. Smits, Jonas Van Audenaerde
Summary: PDAC is a leading cause of cancer related death, with urgent need for effective therapies. Aberrant activation of the Hh signaling pathway in PDAC prompts it as a possible target for treatment, despite ongoing debate on its clinical benefits.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Pharmacology & Pharmacy
Alexander G. Raufi, Nicholas R. Liguori, Lindsey Carlsen, Cassandra Parker, Liz Hernandez Borrero, Shengliang Zhang, Xiaobing Tian, Anna Louie, Lanlan Zhou, Attila A. Seyhan, Wafik S. El-Deiry
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with slow progress towards effective therapy, indicating an urgent need for novel treatment approaches, with autophagy potentially being a promising therapeutic target.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Danyang Ji, Jia-Hao Yuan, Shuo-Bin Chen, Jia-Heng Tan, Chun Kit Kwok
Summary: G-quadruplexes (G4) are unique nucleic acid structures with diverse conformations. In this study, we developed a novel method, G4-SELEX-Seq, to select an L-RNA aptamer with high binding selectivity to a specific G4 conformation. Our results demonstrate the potential applications of this aptamer in controlling DNA replication and gene expression. This research provides a valuable tool for targeting G4 conformations and regulating G4-mediated biological processes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Nicolas A. Fraunhoffer, Daniel Closa, Emma Folch-Puy, Analia Meilerman Abuelafia, Ezequiel Luis Calvo, Eduardo Chuluyan, Juan Iovanna
Summary: The study demonstrates that REG3 beta plays a role in promoting PDAC progression by over-activating CTGF, making it a promising therapeutic target. The far microenvironment, producing active secretory factors, is essential for PDAC progression and some of these factors could be utilized as therapeutic targets.
Article
Biochemistry & Molecular Biology
Hweixian Leong Penny, Je Lin Sieow, Sin Yee Gun, Mai Chan Lau, Bernett Lee, Jasmine Tan, Cindy Phua, Florida Toh, Yvonne Nga, Wei Hseun Yeap, Baptiste Janela, Dilip Kumar, Hao Chen, Joe Yeong, Justin A. Kenkel, Angela Pang, Diana Lim, Han Chong Toh, Tony Lim Kiat Hon, Christopher Johnson, Hanif Javanmard Khameneh, Alessandra Mortellaro, Edgar G. Engleman, Olaf Rotzschke, Florent Ginhoux, Jean-Pierre Abastado, Jinmiao Chen, Siew Cheng Wong
Summary: Inflammation in the tumor microenvironment promotes disease progression in PDAC. Macrophages from tumor-bearing individuals exhibit elevated glycolysis, and macrophage-specific deletion of GLUT1 reduces tumor burden significantly. Pharmacological inhibition of GLUT1 can decrease tumor burden and improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiao Wu, Jian-Hui Li, Long Xu, Ya-Xiong Li, Xiao-Xu Zhu, Xi-Yu Wang, Xingmei Wu, Wei Zhao, Xuhao Ni, Xiao-Yu Yin
Summary: This study identified SENP3 as a potential suppressor of PDAC progression through its interaction with DKC1 and catalyzing the deSUMOylation of DKC1. Overexpression of DKC1 counteracted the anti-metastasis effect of SENP3, and elevated levels of DKC1 were associated with a poor prognosis in PDAC patients.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Oncology
Ahmad Ali, Ugo Chianese, Chiara Papulino, Antonella Toraldo, Mawada Elmagboul Abdalla Abakar, Eugenia Passaro, Rosario Cennamo, Nunzio Del Gaudio, Lucia Altucci, Rosaria Benedetti
Summary: This article describes the metabolic features of pancreatic ductal adenocarcinoma and discusses how this could be exploited as a weakness for clinical interventions. Metabolism plays a crucial role in the development of PDAC, and interventions on bioenergetic circuits could potentially reduce its aggressiveness.
Review
Oncology
Siddharth Mehra, Nilesh Deshpande, Nagaraj Nagathihalli
Summary: Pancreatic cancer has a low survival rate and strong resistance to treatment, making targeted inhibition of the PI3K/Akt/mTOR pathway crucial for reducing tumor burden and improving survival. Targeted therapy against PI3K signaling has shown significant impact on modulating tumor-stromal-immune interactions within the microenvironment of pancreatic cancer.
Review
Oncology
Nebojsa Skorupan, Mayrel Palestino Dominguez, Samuel L. Ricci, Christine Alewine
Summary: This review discusses the diverse cell composition and interactions in pancreatic cancer tumors, as well as the impact on cancer cell growth and treatment responses. It also introduces new drug therapies and clinical trials.
Review
Pharmacology & Pharmacy
Ziba Lotfi, Shiva Najjary, Fariba Lotfi, Mohammad Amini, Amir Baghbanzadeh, Darya Javad Rashid, Elmira Roshani Asl, Behzad Baradaran, Ahad Mokhtarzadeh
Summary: Pancreatic cancer is a deadly cancer with low survival rates, mainly due to relapse and resistance to treatment. Tumors have a high desmoplastic stroma, affecting growth and spread. Genetic studies show common molecular features and mutations in key genes in PC development.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, T. Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Weiming Yang, Jianbo Pan, Bo Wen, Yongchao Dou, Wen Jiang, Yuxing Liao, Zhiao Shi, Nadezhda Terekhanova, Song Cao, Rita Jui-Hsien Lu, Yize Li, Ruiyang Liu, Houxiang Zhu, Peter Ronning, Yige Wu, Matthew A. Wyczalkowski, Hariharan Easwaran, Ludmila Danilova, Arvind Singh Mer, Seungyeul Yoo, Joshua M. Wang, Wenke Liu, Benjamin Haibe-Kains, Mathangi Thiagarajan, Scott D. Jewell, Galen Hostetter, Chelsea J. Newton, Qing Kay Li, Michael H. Roehr, David Fenyo, Pei Wang, Alexey Nesvizhskii, D. R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang
Summary: This study conducted comprehensive proteogenomic analysis of PDAC to understand the molecular alterations that drive oncogenesis. Multiple analyses were performed on tissues from patients, providing valuable resources for early detection and identification of therapeutic targets.
Review
Biochemistry & Molecular Biology
Nausika Betriu, Juan Bertran-Mas, Anna Andreeva, Carlos E. Semino
Summary: Syndecans, a subfamily of proteoglycans, play critical roles in various physiological processes and have implications in disease progression. Their interactions with other macromolecules contribute to normal cellular functions and disease pathogenesis.
Article
Chemistry, Physical
Christopher R. Below, Joanna Kelly, Alexander Brown, Jonathan D. Humphries, Colin Hutton, Jingshu Xu, Brian Y. Lee, Celia Cintas, Xiaohong Zhang, Victor Hernandez-Gordillo, Linda Stockdale, Matthew A. Goldsworthy, Joe Geraghty, Lucy Foster, Derek A. O'Reilly, Barbara Schedding, Janet Askari, Jessica Burns, Nigel Hodson, Duncan L. Smith, Catherine Lally, Garry Ashton, David Knight, Aleksandr Mironov, Antonia Banyard, Johannes A. Eble, Jennifer P. Morton, Martin J. Humphries, Linda G. Griffith, Claus Jorgensen
Summary: A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin-integrin interactions in their growth.
Review
Oncology
Victor Hugo Fonseca de Jesus, Maria Cecilia Mathias-Machado, Joao Paulo Fogacci de Farias, Marcelo Porfirio Sunagua Aruquipa, Alexandre A. Jacome, Renata D'Alpino Peixoto
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with poor prognosis. The discovery of KRAS mutations as a pivotal event in pancreatic carcinogenesis has opened new avenues for targeted therapy. Recent research has provided insights into the different KRAS mutations, their prognostic implications, and therapeutic opportunities. Inhibitors of KRAS signaling, particularly KRAS G12C inhibitors, have shown promise in clinical trials. Overall, understanding the role of KRAS in PDAC offers hope for a significant improvement in treatment outcomes.
Article
Oncology
Bala Prabhakar Girish, Begum Dariya, Mastan Mannarapu, Ganji Purnachandra Nagaraju, Ganji Seeta Rama Raju
Summary: Pancreatic cancer faces challenges from abnormal proliferation of stromal cells, and traditional treatments may cause excessive toxicity to normal cells. Nanotechnology can deliver drugs directly to tumor sites, enhancing treatment efficacy.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Gaia Bellomo, Carolyn Rainer, Valeria Quaranta, Yuliana Astuti, Meirion Raymant, Elzbieta Boyd, Ruth Stafferton, Fiona Campbell, Paula Ghaneh, Christopher M. Halloran, Dean E. Hammond, Jennifer P. Morton, Daniel Palmer, Dale Vimalachandran, Robert Jones, Ainhoa Mielgo, Michael C. Schmid
Summary: This study investigates the reaction of the microenvironment in PDAC liver metastases to chemotherapy and its role in metastatic disease progression after treatment. The researchers found that chemotherapy induces infiltration of proinflammatory macrophages and activates cytotoxic T cells in the liver, but after treatment, neutrophils are recruited to the liver and promote tumor cell regrowth. Disruption of neutrophil infiltration or inhibition of the Gas6/AXL signaling axis in combination with chemotherapy inhibits metastatic growth.
Article
Multidisciplinary Sciences
Katherine G. Zyner, Angela Simeone, Sean M. Flynn, Colm Doyle, Giovanni Marsico, Santosh Adhikari, Guillem Portella, David Tannahill, Shankar Balasubramanian
Summary: This study reveals that G-quadruplexes (G4s), four-stranded DNA secondary structures, are key genomic features linked to cellular differentiation. G4s are highly present in human embryonic stem cells but lost during lineage specification. They are mainly found in enhancers and promoters and are closely associated with transcriptional stabilization of genes involved in essential cellular functions and transitions in histone post-translational modification landscape. Moreover, stabilizing G4s with small molecules delays stem cell differentiation, maintaining a pluripotent-like state. These findings highlight the importance of G4s as epigenetic features coupled to stem cell pluripotency and differentiation.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Gastroenterology & Hepatology
Seth B. Coffelt, Jennifer P. Morton
Article
Biochemistry & Molecular Biology
Andrew M. Kidger, Mark K. Saville, Linda K. Rushworth, Jane Davidson, Julia Stellzig, Motoharu Ono, Ludwig A. Kuebelsbeck, Klaus-Peter Janssen, Bernhard Holzmann, Jennifer P. Morton, Owen J. Sansom, Christopher J. Caunt, Stephen M. Keyse
Summary: DUSP5 and DUSP6 are negative regulators of RAS/ERK signaling pathway. Deletion of either Dusp5 or Dusp6 promotes pancreatic hyperplasia, acinar to ductal metaplasia, and pre-neoplastic pancreatic intraepithelial neoplasia in a mouse model of KRAS-driven pancreatic cancer. However, as time progresses, pancreatic hyperplasia is reversed with atrophy of pancreatic tissue and weight loss observed in animals lacking either DUSP5 or DUSP6. These findings suggest that DUSP5 and DUSP6 have partially non-redundant roles in suppressing oncogenic KRAS signaling, thereby retarding tumor progression.
Article
Oncology
Nur Faezah Binti Ismail, Mona Foth, Amal Rahil Elgaddafi Yousef, Ningxuan Cui, Joshua D. G. Leach, Thomas Jamieson, Saadia A. Karim, Jonathan M. Salmond, Jennifer P. Morton, Tomoko Iwata
Summary: CXCR2 plays a protective role in bladder cancer tumorigenesis by suppressing acute inflammation. The use of CXCR2 inhibitors in bladder cancer treatment may need to consider the immune suppressive status.
Correction
Biochemistry & Molecular Biology
Abigail S. Coetzee, Edward P. Carter, Lucia Rodriguez-Fernandez, James Heward, Qiaoying Wang, Saadia A. Karim, Lina Boughetane, Christopher Milton, Firat Uyulur, Jennifer P. Morton, Hemant M. Kocher, Richard P. Grose
Article
Biochemistry & Molecular Biology
Abigail S. Coetzee, Edward P. Carter, Lucia Rodriguez-Fernandez, James Heward, Qiaoying Wang, Saadia A. Karim, Lina Boughetane, Christopher Milton, Firat Uyulur, Jennifer P. Morton, Hemant M. Kocher, Richard P. Grose
Summary: Pancreatic stellate cells (PSCs) play a crucial role in the treatment-refractory desmoplastic phenotype of pancreatic ductal adenocarcinoma (PDAC) and understanding their effects on tumor growth is crucial. By studying PSC-cancer cell interactions in 3D models, researchers discovered that nuclear FGFR1 is critical for PSC-led invasion of cancer cells. FGFR1 regulates the transcription of NRG1, which in turn promotes invasion through an ERBB2/4 heterodimer. Inhibiting FGFR reduces local invasion in pancreatic tumors, suggesting FGFR and NRG1 as potential targets for PDAC therapy.
Article
Biology
Fares Z. Najar, Evan Linde, Chelsea L. Murphy, Veniamin A. Borin, Huan Wang, Shozeb Haider, Pratul K. Agarwal
Summary: COVID-19 pandemic caused by rapidly mutating and highly transmissible SARS-CoV-2 virus has underscored the importance of preparedness strategies in responding to current and future outbreaks. Real-time genomic surveillance, particularly through mutation analysis of viral proteins, provides a method for predicting surges in infection cases in advance. This approach, applicable to other pathogens as well, offers valuable insights for effective containment measures.
Article
Oncology
Declan Whyte, George Skalka, Peter Walsh, Ania Wilczynska, Nikki R. Paul, Claire Mitchell, Colin Nixon, William Clarke, Martin Bushell, Jennifer P. Morton, Daniel J. Murphy, Nathiya Muthalagu
Summary: The AMPK-related kinase NUAK1 has been identified as a potential vulnerability in MYC-dependent cancer, but its biological roles and the types of cancer that require NUAK1 are poorly understood. Although small-molecule NUAK inhibitors have been developed, their optimal use and potential toxicities are still undetermined.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ahmed A. Ahmed, William Greenhalf, Daniel H. Palmer, Nicole Williams, Jenny Worthington, Tariq Arshad, Shozeb Haider, Effrosyni Alexandrou, Dilek Guneri, Zoe A. E. Waller, Stephen Neidle
Summary: The naphthalene diimide compound QN-302 exhibits high anti-proliferative activity in pancreatic cancer cell lines and anti-tumor activity in several experimental models for the disease. It downregulates the expression of S100P gene and protein, which is involved in key pathways in human cancers and has been identified as a potential biomarker in pancreatic cancer.
Article
Biochemical Research Methods
Daniel J. Nieves, Jeremy A. Pike, Florian Levet, David J. Williamson, Mohammed Baragilly, Sandra Oloketuyi, Ario de Marco, Juliette Griffie, Daniel Sage, Edward A. K. Cohen, Jean-Baptiste Sibarita, Mike Heilemann, Dylan M. Owen
Summary: This study compares the performance of seven algorithms for cluster analysis of single-molecule localization microscopy data. The results provide a framework for comparing these methods and guide users to the best tools. Cluster analysis is an effective method for extracting meaningful information from single-molecule localization microscopy data, but there is no consensus framework for evaluating the performance of different algorithms. This study proposes a systematic approach and evaluation metrics based on simulated conditions to score the success of clustering algorithms.
Article
Multidisciplinary Sciences
James R. W. Conway, Sean C. Warren, Young-Kyung Lee, Andrew T. McCulloch, Astrid Magenau, Victoria Lee, Xanthe L. Metcalf, Janett Stoehr, Katharina Haigh, Lea Abdulkhalek, Cristian S. Guaman, Daniel A. Reed, Kendelle J. Murphy, Brooke A. Pereira, Pauline Melenec, Cecilia Chambers, Sharissa L. Latham, Helen Lenthall, Elissa K. Deenick, Yuanqing Ma, Tri Phan, Elgene Lim, Anthony M. Joshua, Stacey Walters, Shane T. Grey, Yan-Chuan Shi, Lei Zhang, Herbert Herzog, David R. Croucher, Andy Philp, Colinda L. G. J. Scheele, David Herrmann, Owen J. Sansom, Jennifer P. Morton, Antonella Papa, Jody J. Haigh, Max Nobis, Paul Timpson
Summary: Aberrant AKT activation is implicated in various diseases, and therefore targeting AKT has become a significant approach for disease treatment. In this study, we developed an Akt-FRET biosensor mouse that enables the monitoring of AKT activity in live tissues. We demonstrated the sensitivity of this biosensor mouse in different cancer models and showed its suitability for evaluating drug response. Additionally, we observed real-time dynamics of AKT activation in diverse tissues, indicating the broad preclinical applications of this biosensor mouse for studying AKT dynamics in vivo.
Article
Cell Biology
Naiara Perurena, Rebecca Lock, Rachel A. Davis, Srivatsan Raghavan, Natalie F. Pilla, Raymond Ng, Patrick Loi, Caroline J. Guild, Abigail L. Miller, Ewa Sicinska, James M. Cleary, Douglas A. Rubinson, Brian M. Wolpin, Nathanael S. Gray, Sandro Santagata, William C. Hahn, Jennifer P. Morton, Owen J. Sansom, Andrew J. Aguirre, Karen Cichowski
Summary: Pancreatic ductal adenocarcinomas (PDACs) with KRAS mutations are often resistant to MEK inhibitors. This study reveals that MEK inhibitors upregulate Mcl-1 through its association with USP9X, leading to cell survival. Mcl-1 inhibitors and CDK inhibitors can prevent this response and induce tumor regression when combined with MEK inhibitors. USP9X is identified as a potential therapeutic target.
CELL REPORTS MEDICINE
(2023)
Review
Oncology
Simon T. Barry, Dmitry I. Gabrilovich, Owen J. Sansom, Andrew D. Campbell, Jennifer P. Morton
Summary: Myeloid cells in the tumour microenvironment have a significant impact on tumour progression, making them a key target for clinical therapies. However, large-scale clinical trials targeting these cells have had limited success. Understanding the specific functions and roles of different myeloid cell subpopulations within the tumour microenvironment could improve the design of successful clinical trials for myeloid-targeting therapies.
NATURE REVIEWS CANCER
(2023)
Meeting Abstract
Oncology
Jessica Senior, Amanda Dalby, Joao Correia, Jeremy Pike, Kayley Jaworska, Steve Thomas, Alan Smith, Anke Bruning-Richardson
