Review
Pharmacology & Pharmacy
Roisin Daly, Lorraine O'Driscoll
Summary: Extracellular vesicles in the bloodstream could serve as important sources of biomarkers for breast cancer, but the current methods for isolating pure EVs are relatively complex. Research is underway to identify simpler and more selective EV extraction methods, with hope of finding effective biomarkers.
DRUG DISCOVERY TODAY
(2021)
Article
Pharmacology & Pharmacy
Yongmei Zhao, Yuanlin Zheng, Yan Zhu, Yi Zhang, Hongyan Zhu, Tianqing Liu
Summary: This study developed a specific drug delivery system based on M1 macrophage-derived exosomes for pancreatic cancer with chemoresistance. The nanoformulation combining GEM and DFX in M1Exo significantly enhanced therapeutic efficacy against GEM-resistant cancer cells.
Review
Oncology
Naotake Funamizu, Masahiko Honjo, Kei Tamura, Katsunori Sakamoto, Kohei Ogawa, Yasutsugu Takada
Summary: This review summarizes the current evidence for the role of microRNAs (miRNAs) in the mechanism of chemoresistance in pancreatic cancer. Pancreatic cancer has a poor prognosis due to its late discovery, aggressive nature, and chemoresistance. Aberrant miRNAs have been found to induce chemoresistance in pancreatic cancer, but the exact molecular mechanisms are still unclear. Novel biomarkers and therapeutic strategies for chemoresistance are urgently needed to improve patient outcomes.
Article
Medicine, General & Internal
Annalisa Comandatore, Benoit Immordino, Rita Balsano, Mjriam Capula, Ingrid Garajova, Joseph Ciccolini, Elisa Giovannetti, Luca Morelli
Summary: This review summarizes the role of exosomes in pancreatic ductal adenocarcinoma (PDAC) resistance, focusing on their impact on drug resistance pathways, as well as their potential as biomarkers. The study highlights the influence of exosomes on specific determinants of drug activity and discusses the modulation of apoptotic pathways, cellular metabolism, and oncogenic miRNA. The integration of preclinical and clinical data supports the use of exosome research in predicting individual tumor resistance and guiding innovative therapeutic strategies to overcome drug resistance.
Article
Oncology
Huizhi Wang, Jingyu Min, Chunhui Xu, Yawen Liu, Zhengyue Yu, Aihua Gong, Min Xu
Summary: Recent studies have shown that hypoxia-induced exosomes play a role in tumor progression and drug resistance. This study investigated the impact of hypoxia-induced tumor-derived exosomes (Hexo) on stemness and resistance to gemcitabine in pancreatic cancer cells, as well as the underlying molecular mechanisms. The results demonstrated that Hexo enhanced stemness and resistance to gemcitabine in pancreatic cancer cells by inactivating the Hippo/YAP pathway through the transfer of exosomal lncROR. Therefore, exosomal lncROR might be a potential target for chemotherapy in pancreatic cancer.
Article
Genetics & Heredity
Takahiro Seimiya, Motoyuki Otsuka, Takuma Iwata, Eri Tanaka, Kazuma Sekiba, Chikako Shibata, Masaru Moriyama, Ryo Nakagawa, Reo Maruyama, Kazuhiko Koike
Summary: A large-scale circRNA profiling analysis was conducted in PDAC tissues using circular RNA-specific RNA sequencing, identifying over 40,000 previously unknown circRNAs, some of which were upregulated in PDAC tissues. A novel circRNA, named circPDAC RNA, was found to be upregulated in PDAC but not expressed in normal human cells, serving as a potential biomarker for cancers including PDAC.
JOURNAL OF HUMAN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Lily M. Channon, Victoria M. Tyma, Zhihong Xu, David W. Greening, Jeremy S. Wilson, Chamini J. Perera, Minoti V. Apte
Summary: This review provides an overview of the role of extracellular vesicles (EVs) in the pathobiology of pancreatic cancer, as well as the molecular mechanisms mediated by EVs and their cargo in pancreatic cancer progression. EVs offer stability and act as a form of intercellular communication to regulate the function and phenotype of recipient cells.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Medicine, Research & Experimental
V. A. Subramanian, Ravindra Kumar Bairwa, Pradeep Kumar Sharma, Bhawana Bissa
Summary: This article discusses the roles of autophagy and exosomes in the cancer cell's adaptation to the tumor microenvironment and how the two pathways are coordinately regulated to facilitate cancer cell survival.
Article
Oncology
Jie Yang, Yixuan Zhang, Xin Gao, Yue Yuan, Jing Zhao, Siqi Zhou, Hui Wang, Lei Wang, Guifang Xu, Xihan Li, Pin Wang, Xiaoping Zou, Dongming Zhu, Ying Lv, Shu Zhang
Summary: This study demonstrated that proteins isolated from plasma-derived exosomes can serve as ideal non-invasive biomarkers for the clinical diagnosis of pancreatic cancer based on proteomic profiling. Exosomal ALIX combined with CA199 has great potential in detecting pancreatic cancer, especially in distinguishing early-stage patients from advanced-stage patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yuhan Yang, Haitao Gu, Kundong Zhang, Zengya Guo, Xiaofeng Wang, Qingyun Wei, Ling Weng, Xuan Han, Yan Lv, Meng Cao, Peng Cao, Chen Huang, Zhengjun Qiu
Summary: This study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms. Exosomal ACADM was found to be strongly correlated with gemcitabine sensitivity in vivo and can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. ACADM was also observed to regulate the gemcitabine response by affecting ferroptosis through GPX4 and mevalonate pathways.
Review
Biochemistry & Molecular Biology
Susmita Barman, Iram Fatima, Amar B. Singh, Punita Dhawan
Summary: Despite advancements in clinical management, pancreatic cancer remains deadly due to late detection and high metastatic properties. Pancreatic cancer stem cells have been found to play a crucial role in tumorigenesis, progression, and chemoresistance, but targeting them effectively remains a challenge due to cancer heterogeneity and complex signaling pathways regulating PC progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Zhengjun Lin, Yuqiao Ji, Jian Zhou, Guoqing Li, Weifeng Liu, Zhihong Li, Tang Liu
Summary: Despite advances in cancer treatment, resistance to therapy remains a major obstacle. Circular RNAs (circRNAs) are biomolecules with a closed loop structure that can be transferred to tumor cells through exosomes, influencing cancer behavior and therapy resistance. Aberrantly expressed exosomal circRNAs have been found to mediate therapy resistance, making them potential therapeutic targets. This review explores the mechanisms of exosomal circRNAs in modulating cancer therapy resistance and discusses their potential as clinical biomarkers and therapeutic targets in cancer management.
Article
Chemistry, Analytical
Ping Li, Jie Wang, Mengqiu Gao, Jue Wang, Yi Ma, Yueqing Gu
Summary: Extracellular vesicles (EVs) have emerged as a promising tumor biomarker, offering benefits for cancer diagnosis, but the practicality of EV assays remains challenging due to various factors. A membrane-based biosensor has been developed for precise and sensitive EV identification, integrating EV capture and detection based on EV membrane features, showing great potential for clinical prostate cancer diagnosis.
ANALYTICAL CHEMISTRY
(2021)
Article
Biology
Benediktas Kurlinkus, Marija Ger, Algirdas Kaupinis, Eugenijus Jasiunas, Mindaugas Valius, Audrius Sileikis
Summary: This study identified CEACAM6 as a promising new biomarker for pancreatic cancer, with significant prognostic value and prediction of chemoresistance properties, enabling the improvement of individualised approaches to patients with this disease.
Article
Chemistry, Analytical
Amy Makler, Ramaswamy Narayanan, Waseem Asghar
Summary: Exosomal miRNA may be used for early detection of PDAC and potentially differentiate patients with chronic pancreatitis, neoplasms, and PDAC. The study identified 18 miRNA with strong potential, and 7 mature miRs showed statistical significance in exosomal RNA.
Review
Biochemistry & Molecular Biology
Maximilian Brunner, Zhiyuan Wu, Christian Krautz, Christian Pilarsky, Robert Gruetzmann, Georg F. Weber
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Siyuan Zeng, Marina Poettler, Bin Lan, Robert Gruetzmann, Christian Pilarsky, Hai Yang
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Endocrinology & Metabolism
Hassan Mziaut, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna McChord, Kamal Chowdhury, Philippe Ravassard, Klaus-Peter Knoch, Christian Krautz, Juergen Weitz, Robert Gruetzmann, Christian Pilarsky, Michele Solimena, Stephan Kersting
MOLECULAR METABOLISM
(2020)
Article
Cell Biology
Holly Brunton, Giuseppina Caligiuri, Richard Cunningham, Rosie Upstill-Goddard, Ulla-Maja Bailey, Ian M. Garner, Craig Nourse, Stephan Dreyer, Marc Jones, Kim Moran-Jones, Derek W. Wright, Viola Paulus-Hock, Colin Nixon, Gemma Thomson, Nigel B. Jamieson, Grant A. McGregor, Lisa Evers, Colin J. McKay, Aditi Gulati, Rachel Brough, Ilirjana Bajrami, Stephen J. Pettitt, Michele L. Dziubinski, Simon T. Barry, Robert Gruetzmann, Robert Brown, Edward Curry, Marina Pajic, Elizabeth A. Musgrove, Gloria M. Petersen, Emma Shanks, Alan Ashworth, Howard C. Crawford, Diane M. Simeone, Fieke E. M. Froeling, Christopher J. Lord, Debabrata Mukhopadhyay, Christian Pilarsky, Sean E. Grimmond, Jennifer P. Morton, Owen J. Sansom, David K. Chang, Peter J. Bailey, Andrew Biankin
Article
Medicine, General & Internal
Melanie Langheinrich, Stefan Wirtz, Barbara Kneis, Matthias M. Gittler, Olaf Tyc, Robert Schierwagen, Maximilian Brunner, Christian Krautz, Georg F. Weber, Christian Pilarsky, Jonel Trebicka, Abbas Agaimy, Robert Grutzmann, Stephan Kersting
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Oncology
Ali Al-Fatlawi, Negin Malekian, Sebastian Garcia, Andreas Henschel, Ilwook Kim, Andreas Dahl, Beatrix Jahnke, Peter Bailey, Sarah Naomi Bolz, Anna R. Poetsch, Sandra Mahler, Robert Gruetzmann, Christian Pilarsky, Michael Schroeder
Summary: The study identified predictive RNA variants from blood samples of patients with pancreatic diseases, combining them with CA19-9 for deep learning to differentiate pancreatic cancer from chronic pancreatitis with high accuracy. This approach has the potential to greatly improve noninvasive clinical diagnosis and early treatment of pancreatic cancer.
Article
Oncology
Raphaela Schwappacher, Walburga Dieterich, Dejan Reljic, Christian Pilarsky, Debabrata Mukhopadhyay, David K. Chang, Andrew Biankin, Juergen Siebler, Hans J. Herrmann, Markus F. Neurath, Yurdagul Zopf
Summary: Exercise-induced cytokines in serum from advanced-stage pancreatic cancer patients inhibit cancer cell growth and migration, and induce cancer cell death. This study provides new insights into the cancer-protective function of exercise in pancreatic cancer and supports the use of sport therapies for cancer patients.
Article
Cell Biology
Ujjwal Mukund Mahajan, Ahmed Alnatsha, Qi Li, Bettina Oehrle, Frank-Ulrich Weiss, Matthias Sendler, Marius Distler, Waldemar Uhl, Tim Fahlbusch, Elisabetta Goni, Georg Beyer, Ansgar Chromik, Markus Bahra, Fritz Klein, Christian Pilarsky, Robert Gruetzmann, Markus M. Lerch, Kirsten Lauber, Nicole Christiansen, Beate Kamlage, Ivonne Regel, Julia Mayerle
Summary: The study identified three metabolic PDAC subtypes associated with distinct complex lipid patterns through plasma metabolome analysis, revealing the heterogeneity of PDAC patients and laying the foundation for sphingolipid metabolism research in PDAC.
Article
Oncology
Bin Lan, Siyuan Zeng, Shuman Zhang, Xiaofan Ren, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Benjamin Frey, Nathalie Britzen-Laurent, Robert Gruetzmann, Nils Cordes, Christian Pilarsky
Summary: Pancreatic cancer is the fourth leading cause of cancer-related deaths in Western countries. Radiation therapy has not yielded satisfactory results in treating pancreatic cancer, and understanding radioresistance mechanisms and developing new therapeutic targets have become major challenges. In this study, the researchers used CRISPR-Cas9 screening and 3D cell culture to identify DYRK1A as a sensitive target for radiotherapy in pancreatic cancer. Furthermore, they showed that DYRK1A-targeted inhibitors could enhance the efficacy of radiotherapy. These findings support the use of CRISPR-Cas9 screening to identify novel therapeutic targets and develop strategies to improve radiotherapy efficacy in pancreatic cancer.
Article
Oncology
Hai Yang, Bin Liu, Dongxue Liu, Zhirong Yang, Shuman Zhang, Pengyan Xu, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Nathalie Britzen-Laurent, Robert Gruetzmann, Christian Pilarsky
Summary: Pancreatic cancer is a highly lethal cancer with limited treatment options. Chemotherapy, especially with gemcitabine, is the primary choice for patients; however, chemoresistance presents a significant challenge to its effectiveness. In this study, we used genome-wide CRISPR/Cas9 screening to identify DCK and CCNL1 as genes contributing to gemcitabine resistance in pancreatic cancer. Furthermore, we explored the mechanism of CCNL1-related resistance and found that the loss of CCNL1 activates the ERK/AKT/STAT3 pathway, leading to resistance to gemcitabine.
Review
Chemistry, Analytical
Yusong Wu, Yuqing Wang, Yanjun Lu, Xiaomei Luo, Yinghong Huang, Ting Xie, Christian Pilarsky, Yuanye Dang, Jianye Zhang
Summary: This review provides an overview of the conventional methods and microfluidic-based technologies for exosome separation, with a focus on the efficiency of exosome isolation by microfluidic devices. Additionally, advances in integrated microfluidics technologies for exosome separation and analysis are introduced.
Article
Oncology
Hang He, Shuman Zhang, Hai Yang, Pengyan Xu, Isabella Kutschick, Susanne Pfeffer, Nathalie Britzen-Laurent, Robert Gruetzmann, Deliang Fu, Christian Pilarsky
Summary: This study identified PCSK6 as a critical gene involved in liver metastasis in pancreatic cancer and investigated its biological functions and molecular mechanisms using CRISPR/Cas9 technology. It was found that inactivation of PCSK6 could efficiently suppress liver metastasis, suggesting its potential as a novel therapeutic target for liver metastasis in pancreatic cancer.
Article
Chemistry, Physical
Jonas Dinter, Ralf. P. P. Friedrich, Hai Yang, Christian Pilarsky, Harald Mangge, Marina Poettler, Christina Janko, Christoph Alexiou, Stefan Lyer
Summary: Pancreatic ductal adenocarcinoma is a difficult-to-treat cancer with poor long-term survival rates. In this study, a 3D cell culture model of human pancreatic ductal adenocarcinoma was used to investigate the potential use of superparamagnetic iron oxide nanoparticles (SPIONs) as a drug delivery system for the chemotherapeutic agent mitoxantrone (MTO). The results showed that MTO-loaded SPIONs induced cell death in tumor spheroids, with increased uptake in spheroids with a SMAD4 mutation. This suggests that MTO-loaded SPIONs could be a promising approach for treating pancreatic ductal adenocarcinomas.
