Article
Medicine, General & Internal
Neus Martinez-Bosch, Helena Cristobal, Mar Iglesias, Meritxell Gironella, Luis Barranco, Laura Visa, Domenico Calafato, Silvia Jimenez-Parrado, Julie Earl, Alfredo Carrato, Noemi Manero-Ruperez, Mireia Moreno, Albert Morales, Carmen Guerra, Pilar Navarro, Pablo Garcia de Frutos
Summary: This study explores the use of sAXL as a biomarker for pancreatic ductal adenocarcinoma (PDAC). The research shows that AXL is increased in PDAC tissues and plasma sAXL concentrations are elevated in PDAC patients. Higher levels of AXL are associated with lower overall survival. sAXL performs better than CA19-9 in discriminating between PDAC and chronic pancreatitis (CP). The combination of sAXL and CA19-9 improves the diagnostic value.
Review
Pharmacology & Pharmacy
Xufeng Tao, Hong Xiang, Yue Pan, Dong Shang, Junchao Guo, Ge Gao, Gary Guishan Xiao
Summary: PDAC is a highly malignant lethal disease that is caused by pancreatitis and involves various pancreatic cells interacting in an inflammation-mediated microenvironment. Understanding the players and their interactions is crucial for the development of effective therapies.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Oncology
Meilin Xue, Minmin Shi, Junjie Xie, Jun Zhang, Lingxi Jiang, Xiaxing Deng, Chenghong Peng, Baiyong Shen, Hong Xu, Hao Chen
Summary: This study identified tsRNAs as potential biomarkers for early detection of PDAC, with tsRNA-ValTAC-41 and tsRNA-MetCAT-37 showing high diagnostic accuracy and predictive performance in the serum of PDAC patients. These tsRNAs could be promising candidates for the development of highly sensitive and noninvasive biomarkers for PDAC diagnosis.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Review
Oncology
Ryan McGowan, Aine Sally, Anthony McCabe, Brian Michael Moran, Karen Finn
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and deadly cancer often diagnosed at a late stage due to nonspecific symptoms and a lack of reliable biomarkers. This review highlights the potential use of circulating nucleic acid-based biomarkers for early detection and monitoring of PDAC. However, the lack of prognostic biomarkers remains a challenge for assessing treatment efficacy.
Article
Gastroenterology & Hepatology
Andrea Costamagna, Dora Natalini, Maria del Pilar Camacho Leal, Matilde Simoni, Luca Gozzelino, Paola Cappello, Francesco Novelli, Chiara Ambrogio, Paola Defilippi, Emilia Turco, Elisa Giovannetti, Emilio Hirsch, Sara Cabodi, Miriam Martini
Summary: High expression of p130Cas is associated with higher histologic grade and poor prognosis in PDAC. Deletion of p130Cas inhibits acinar-derived tumorigenesis and progression by suppressing PI3K-AKT signaling. Targeting the PI3K pathway may be a rational therapeutic strategy for tumors with high expression of p130Cas.
Review
Biochemistry & Molecular Biology
I. Gede Putu Supadmanaba, Giulia Mantini, Ornella Randazzo, Mjriam Capula, Ittai B. Muller, Stella Cascioferro, Patrizia Diana, Godefridus J. Peters, Elisa Giovannetti
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with late diagnosis and chemoresistance, but studies on the interaction between splicing and miRNA offer new possibilities for innovative treatments by targeting therapeutic targets and biomarkers.
Review
Chemistry, Medicinal
Jul Dardare, Andrea Witz, Jean-Louis Merlin, Agathe Bochnakian, Paul Toussaint, Pauline Gilson, Alexandre Harle
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, mainly due to late-stage diagnosis. EMT plays a significant role in PDAC, not only related to cancer progression and metastasis, but also potentially becoming a new therapeutic target.
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.
Article
Oncology
Nayela N. Chowdhury, Yi Yang, Ananya Dutta, Michelle Luo, Zimu Wei, Sara R. Abrahams, Alexey S. Revenko, Fenil Shah, Lindsey A. Miles, Robert J. Parmer, Bas de Laat, Alisa S. Wolberg, James P. Luyendyk, Melissa L. Fishel, Matthew J. Flick
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. Primary fibrinolytic protease plasminogen promotes PDAC tumor growth and metastatic potential through engaging plasminogen receptors on tumor cells.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Ailin Wei, Huiling Zhao, Xue Cong, Linyao Wang, Yiyang Chen, Juxiang Gou, Ziyi Hu, Xiuying Hu, Yali Tian, Ka Li, Yufeng Deng, Haojiang Zuo, Mei Rosemary Fu
Summary: This study investigated the association between oral mycobiota and pancreatic ductal adenocarcinoma (PDAC). The findings suggest that PDAC patients have increased fungal abundance and decreased fungal diversity compared to healthy controls. Certain fungal species, such as Aspergillus and Cladosporium, showed high classification powers in distinguishing PDAC patients from healthy controls. The findings highlight the potential of using oral mycobiota as a biomarker for early detection and prevention of PDAC.
Article
Gastroenterology & Hepatology
L. Sivapalan, H. M. Kocher, H. Ross-Adams, C. Chelala
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options. Most patients present with advanced disease and are not candidates for surgery. Genomic analyses have identified recurrent alterations in PDAC tumors, but heterogeneity and lack of tumor biopsies for sequencing pose challenges for subtype characterization and biomarker identification. Furthermore, invasive tissue sampling and low tumor cellularity limit the use of molecular profiling in unresectable patients. Alternative sources of analytes for minimally invasive sampling and complementing tissue sequencing are needed.
Review
Oncology
Mahrou Vahabi, Bilal Dehni, Ines Antomas, Elisa Giovannetti, Godefridus J. Peters
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited improvement in mortality rate despite extensive research and clinical trials. There is a need for comprehensive molecular characterization to identify biomarkers for early detection and evaluation of treatment response. MicroRNAs (miRNAs) show promise as stable biomarkers that can be detected in fixed tissues and biofluids, and their deregulation plays a role in the oncogenesis and metastasis of PDAC. Several oncomiRs and TsmiRs have been identified that contribute to chemoresistance in PDAC, and miRNA-based therapy approaches have shown success in vivo. Integrating miRNAs in PDAC treatment holds potential for personalized medicine.
CANCER AND METASTASIS REVIEWS
(2023)
Review
Medicine, General & Internal
Natalia Michalak, Ewa Malecka-Wojciesko
Summary: This study summarizes the known modifiable risk factors for pancreatic ductal adenocarcinoma (PDAC) as well as recent reports. PDAC has a late diagnosis and poor prognosis, making accurate analysis of risk factors crucial. The incidence of PDAC is increasing, with the lowest five-year survival rate among all tumors. The impact of cigarette smoking, alcohol consumption, and chronic pancreatitis in increasing the risk of PDAC is continuously confirmed, while emerging reports focus on the influence of lifestyle factors and hepatotropic viruses.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Neurosciences
Bo Ni, Yiqing Yin, Zekun Li, Junjin Wang, Xiuchao Wang, Kaiyuan Wang
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with late diagnosis and therapy resistance. The peripheral nerve has been found to play an important role in tumor growth and immune escape in the tumor microenvironment. Understanding the crosstalk between the neuronal system and PDAC may provide new insights into tumor progression and potential therapeutic targets.
NEUROSCIENCE BULLETIN
(2023)
Article
Geriatrics & Gerontology
Jie Dong, Jie Yu, Zekun Li, Song Gao, Hongwei Wang, Shengyu Yang, Liangliang Wu, Chungen Lan, Tiansuo Zhao, Chuntao Gao, Zhe Liu, Xiuchao Wang, Jihui Hao
Summary: This study demonstrates a significant correlation between serum IGFBP2 levels, malnutrition, and muscle atrophy in PDAC. The results suggest that serum IGFBP2 level might serve as a promising biomarker and intervention target for severe malnutrition and muscle wasting associated with PDAC.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
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
Biochemistry & Molecular Biology
Dario P. Anobile, Mauro Niso, Adrian Puerta, Stephanie M. Fraga Rodrigues, Francesca S. Abatematteo, Amir Avan, Carmen Abate, Chiara Riganti, Elisa Giovannetti
Summary: A new sigma-2 receptor ligand FA4 was synthesized and evaluated for its anti-proliferative, pro-apoptotic, and anti-migratory activity on PDAC primary cell cultures. The results showed that FA4 effectively inhibited the aggressive and chemoresistant behavior of PDAC, with significant antiproliferative and antimigratory effects.
Review
Pharmacology & Pharmacy
Dario P. Anobile, Giulia Montenovo, Camilla Pecoraro, Marika Franczak, Widad Ait Iddouch, Godefridus J. Peters, Chiara Riganti, Elisa Giovannetti
Summary: Malignant mesothelioma is an aggressive rare cancer associated with asbestos exposure and currently incurable due to drug resistance. The alterations in miRNA and splicing machinery may contribute to chemoresistance. The Notch signaling pathway, frequently deregulated in MMe, is involved in cancer stem cell formation and self-renewal, leading to drug resistance and relapses.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2022)
Article
Oncology
Alessandro Gregori, Cecilia Bergonzini, Mjriam Capula, Giulia Mantini, Fatemeh Khojasteh-Leylakoohi, Annalisa Comandatore, Ghazaleh Khalili-Tanha, Alireza Khooei, Luca Morelli, Amir Avan, Erik H. Danen, Thomas Schmidt, Elisa Giovannetti
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemoresistant cancer, with a stiff stroma surrounding it playing a role in chemoresistance. High expression of the mechanical sensor ITGA2 correlated with a poor prognosis in PDAC patients, and increased matrix stiffness led to the expression of ITGA2 and chemoresistance to gemcitabine. ITGA2 could be a potential therapeutic target to overcome gemcitabine resistance.
Article
Medicine, General & Internal
Lenka N. C. Boyd, Mahsoem Ali, Mariska M. G. Leeflang, Giorgio Treglia, Ralph de Vries, Tessa Y. S. Le Large, Marc G. Besselink, Elisa Giovannetti, Hanneke W. M. van Laarhoven, Geert Kazemier
Summary: This study assesses the diagnostic accuracy of newly recognized blood-based protein biomarkers for detecting pancreatic cancer and investigates their added value to CA19-9. The results show that CA19-9 is more accurate than other protein biomarkers in distinguishing pancreatic cancer from benign disease, and the added clinical value of these novel biomarkers is limited.
Review
Biochemistry & Molecular Biology
Federica Borea, Marika A. Franczak, Maria Garcia, Matteo Perrino, Nadia Cordua, Ryszard T. Smolenski, Godefridus J. Peters, Rafal Dziadziuszko, Armando Santoro, Paolo A. Zucali, Elisa Giovannetti
Summary: Malignant Pleural Mesothelioma (MPM) is a rare neoplasm that is usually diagnosed at an advanced stage and requires systemic treatment due to its ineligibility for radical surgery. Chemotherapy has been the standard treatment for 20 years until immune checkpoint inhibitors were introduced. However, the prognosis remains poor, and targeted therapies for MPM have mostly failed in clinical trials. This review aims to explore the potential reasons for treatment failures and determine the need for further research in this area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Calogera Claudia Spagnolo, Giuliana Ciappina, Elisa Giovannetti, Andrea Squeri, Barbara Granata, Chiara Lazzari, Giulia Pretelli, Giulia Pasello, Mariacarmela Santarpia
Summary: In recent years, the development of therapeutic agents targeting actionable oncogenic drivers in metastatic non-small cell lung cancer (NSCLC) has increased. Selective inhibitors, such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have shown promising results in patients with MET deregulation, specifically exon 14 skipping mutations or MET amplification. This review provides an overview of MET signaling pathways, oncogenic alterations, laboratory techniques for detection, clinical data and ongoing studies on MET inhibitors, resistance mechanisms, and potential strategies for improving outcomes in MET-exon 14-altered NSCLC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marika A. Franczak, Oliwia Krol, Gabriela Harasim, Agata Jedrzejewska, Nadia Zaffaroni, Carlotta Granchi, Filippo Minutolo, Amir Avan, Elisa Giovannetti, Ryszard T. Smolenski, Godefridus J. Peters
Summary: Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. In this study, the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration was investigated. The inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were most effective in cells with the highest metabolic modulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Yan Zhou, Yizhen Guo, Maoxin Ran, Wenying Shan, Carlotta Granchi, Elisa Giovannetti, Filippo Minutolo, Godefridus J. Peters, Kin Yip Tam
Summary: This study investigated the anticancer effects of combined inhibition of PDK1 and LDHA in LUAD and its underlying mechanisms. The results showed that the combination of a PDK1 inhibitor and a LDHA inhibitor could synergistically inhibit LUAD growth and suppress tumor growth in vivo. This combination also inhibited cellular migration and colony formation, inducing mitochondrial depolarization and apoptosis in LUAD cells.
Letter
Oncology
Lenka N. C. Boyd, Mahsoem Ali, Jisce R. Puik, Laura L. Meijer, Tessa Y. S. Le Large, Hanneke W. M. van Laarhoven, Elisa Giovannetti, Geert Kazemier
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Mahrou Vahabi, Annalisa Comandatore, Marika A. Franczak, Ryszard T. Smolenski, Godefridus J. Peters, Luca Morelli, Elisa Giovannetti
Summary: Exosomes play a crucial role in intercellular communication and can influence cancer cell behavior and response to treatment. They can transport glycolytic enzymes, leading to altered glucose metabolism and increased tumor progression, survival, immune evasion, and drug resistance. Understanding exosome-mediated cell-to-cell communication may open new therapeutic avenues and facilitate biomarker development, and combining exosome-based-targeted therapies with existing treatments holds promise in overcoming resistance and improving cancer treatment outcomes.
CYTOKINE & GROWTH FACTOR REVIEWS
(2023)
Article
Chemistry, Medicinal
Daniela Carbone, Camilla Pecoraro, Giovanna Panzeca, Geng Xu, Margot S. F. Roeten, Stella Cascioferro, Elisa Giovannetti, Patrizia Diana, Barbara Parrino
Summary: A series of new nortopsentin analogs were successfully synthesized by replacing the central imidazole ring with a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety. The antiproliferative activity of these derivatives was evaluated against pancreatic cancer cell lines, showing significant reduction in cell migration. Cell cycle analysis indicated cell cycle arrest and inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation.
Article
Oncology
Maryam Alaei, Seyedeh Elnaz Nazari, Ghazaleh Pourali, AliReza Asadnia, Mehrdad Moetamani-Ahmadi, Hamid Fiuji, Hamid Tanzadehpanah, Fereshteh Asgharzadeh, Fatemeh Babaei, Fatemeh Khojasteh-Leylakoohi, Ibrahim Saeed Gataa, Mohammad Ali Kiani, Gordon A. Ferns, Alfred King-yin Lam, Seyed Mahdi Hassanian, Majid Khazaei, Elisa Giovannetti, Amir Avan
Summary: In this study, the potential of targeting the enzyme cytochrome P450 (CYP450) using lopinavir/ritonavir in colorectal cancer (CRC) was explored. Experimental methods were employed to assess the effects of lopinavir/ritonavir on CRC, and it was found that inhibiting CYP450 reduced cell proliferation, induced cell death, and suppressed cell migration. Lopinavir/ritonavir also inhibited tumor growth and fibrosis. These findings suggest that targeting CYP450 with lopinavir/ritonavir has therapeutic potential in CRC and further research in this area is needed.
Article
Biochemistry & Molecular Biology
Nabeel Merali, Tarak Chouari, Julien Terroire, Maria-Danae Jessel, Daniel S. K. Liu, James-Halle Smith, Tyler Wooldridge, Tony Dhillon, Jose I. Jimenez, Jonathan Krell, Keith J. Roberts, Timothy A. Rockall, Eirini Velliou, Shivan Sivakumar, Elisa Giovannetti, Ayse Demirkan, Nicola E. Annels, Adam E. Frampton
Summary: The bile microbiome plays an important role in pancreatic ductal adenocarcinoma (PDAC) and can distinguish malignant tumors from benign ones. It was found that the composition of the bile microbiome is altered in patients with PDAC, suggesting that these microbial changes could potentially serve as diagnostic and prognostic biomarkers for PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
