Review
Oncology
Kostas Palamaris, Evangelos Felekouras, Stratigoula Sakellariou
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy characterized by aggressive behavior and resistance to chemotherapy, with emerging evidence pointing to epithelial to mesenchymal transition (EMT) as a key driver of disease progression and drug resistance. EMT allows cancer cells to transition to a more mesenchymal state, contributing to tumor dissemination and chemoresistance in PDAC.
Article
Biochemistry & Molecular Biology
Ella Rimmer, Sadaf Rashid, Igor Kraev, Francesc Miralles, Androulla Elia
Summary: Pancreatic cancer cells release extracellular vesicles that confer resistance to gemcitabine and TRAIL treatment. Removal of these vesicles during treatment may improve the response of pancreatic cancer cells to gemcitabine and TRAIL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Valentina Panzeri, Isabella Manni, Alessia Capone, Chiara Naro, Andrea Sacconi, Silvia Di Agostino, Luisa de Latouliere, Andrea Montori, Emanuela Pilozzi, Giulia Piaggio, Gabriele Capurso, Claudio Sette
Summary: The research revealed that MEX3A plays a significant role in the acquisition and maintenance of chemoresistance by PDAC cells, suggesting it may represent a novel therapeutic target for PDAC.
MOLECULAR ONCOLOGY
(2021)
Review
Oncology
Aine Sally, Ryan McGowan, Karen Finn, Brian Michael Moran
Summary: Pancreatic cancer is a major cause of cancer-related death worldwide, primarily due to delayed diagnosis and resistance to traditional chemotherapy. Delayed diagnosis is often caused by the wide range of non-specific symptoms associated with the disease. Resistance to current chemotherapies, such as gemcitabine, develops due to genetic mutations that are either intrinsic or acquired. This has resulted in poor patient prognosis and justifies the requirement for new targeted therapies. Synthetic lethality approaches targeting specific loss-of-function mutations have shown great potential in pancreatic cancer treatment. Immunotherapies have also yielded promising results and are currently undergoing clinical trials. Monoclonal antibodies, immune checkpoint inhibitors, adoptive cell transfer, and vaccines have shown success in other cancers and could hold the same potential in pancreatic cancer treatment. This review focuses on currently approved therapies, challenges, and future directions in pancreatic cancer therapy, including synthetic lethality approaches, immunotherapy, and clinical trials.
Article
Oncology
Elham Aida Farshadi, Jiang Chang, Bharath Sampadi, Michail Doukas, Freek Van 't Land, Fleur van der Sijde, Eveline E. Vietsch, Joris Pothof, Bas Groot Koerkamp, Casper H. J. van Eijck
Summary: This study investigated the sensitivity and resistance of cancer cells to therapy by generating organoids from resected tumors of patients who received neoadjuvant FOLFIRINOX chemotherapy. The results demonstrated that neoadjuvant FOLFIRINOX-treated organoids displayed resistance to FOLFIRINOX, irinotecan, and oxaliplatin, suggesting that continuing FOLFIRINOX therapy may not be advantageous for these patients. Gene-expression profiles of PDAC organoids identified targetable pathways involved in chemoresistance development, indicating potential for combination therapy strategies.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Maria Laura Gutierrez, Luis Munoz-Bellvis, Alberto Orfao
Summary: Pancreatic ductal adenocarcinoma (PDAC) remains a malignancy with limited therapeutic options due to its heterogeneous molecular profile. Research on genomic heterogeneity of PDAC has shown impacts on disease behavior and treatment, potentially leading to variable patient outcomes.
Article
Oncology
Lishan Fang, Shaojing Chen, Hui Gong, Shaohua Xia, Sainan Guan, Nali Quan, Yajie Li, Chao Zeng, Ya Chen, Jianhang Du, Shuguang Liu
Summary: In this study, a novel UPR-related prognostic signature was identified that accurately predicted survival in patients with PDAC. Multiple immune-related pathways were enriched in the low-risk group, and risk scores in the low-risk group were associated with higher levels of TILs. Furthermore, PDAC cell lines with high UPR-related risk scores or UPR activation were more sensitive to floxuridine.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Yong-Qiang Hua, Ke Zhang, Jie Sheng, Zhou-Yu Ning, Ye Li, Wei-Dong Shi, Lu-Ming Liu
Summary: The study revealed that downregulation of NUCB1 in PDAC patients is associated with poor prognosis, while overexpression of NUCB1 can suppress pancreatic cancer cell proliferation and enhance the effects of gemcitabine. NUCB1 overexpression also inhibits autophagy by controlling ATF6 activity, and METTL3-mediated m(6)A modification is identified as a mechanism for NUCB1 downregulation in PDAC.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Jinsheng Ding, Hui Li, Yang Liu, Yongjie Xie, Jie Yu, Huizhi Sun, Di Xiao, Yizhang Zhou, Li Bao, Hongwei Wang, Chuntao Gao
Summary: This study identified OXCT1 as a key gene leading to GEM resistance in PDAC through the NF-kappa B signaling pathway, with high OXCT1 expression associated with shorter relapse-free survival under GEM treatment. OXCT1 overexpression in PDAC cell lines inhibited apoptosis after GEM treatment, and blocking the NF-kappa B signaling pathway reduced GEM resistance. These findings suggest that OXCT1 could be a potential therapeutic target for patients with PDAC.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ashish Manne, Anup Kasi, Ashwini Kumar Esnakula, Ravi Kumar Paluri
Summary: MUC5AC glycoprotein plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis and drug sensitivity. The mature variants of MUC5AC have prognostic and predictive value, but clinical studies are needed for validation. We propose a MUC5AC signature combining localization, variant composition, and intensity as a reliable marker. Preliminary evidence suggests that mature MUC5AC may predict sensitivity to drugs used in PDAC management, but further large-scale studies are required for validation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Ryan N. Fuller, Janviere Kabagwira, Paul A. Vallejos, Andrew D. Folkerts, Nathan R. Wall
Summary: The study suggests a potential role of survivin splice variants, especially SSV 2 beta, in innate and acquired PDAC chemoresistance. Knockdown of SSVs using siRNA sensitized the GR cells to Gem, indicating their involvement in PDAC chemoresistance.
ONCOTARGETS AND THERAPY
(2022)
Article
Cell Biology
Yu-Ying Chao, Bu-Miin Huang, I-Chen Peng, Pei-Rong Lee, Yi-Shyun Lai, Wen-Tai Chiu, Yi-Syuan Lin, Shih-Chieh Lin, Jung-Hsuan Chang, Pai-Sheng Chen, Shaw-Jenq Tsai, Chia-Yih Wang
Summary: Loss of primary cilia is associated with chemoresistance in pancreatic ductal adenocarcinoma (PDAC). Disruption of primary ciliogenesis sensitizes PDAC cells to cisplatin treatment, indicating a potential therapeutic strategy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Medicine, General & Internal
Daniel J. Fulop, Haley M. Zylberberg, Y. Linda Wu, Anne Aronson, Arielle J. Labiner, Juan Wisnivesky, Deirdre J. Cohen, Keith M. Sigel, Aimee L. Lucas
Summary: This study investigates the association between the use of pre-treatment antibiotics and survival in patients with metastatic pancreatic ductal adenocarcinoma who received first-line gemcitabine or fluorouracil chemotherapy.
Article
Oncology
Marina Roy-Luzarraga, Louise E. Reynolds, Beatriz de Luxan-Delgado, Oscar Maiques, Laura Wisniewski, Emma Newport, Vinothini Rajeeve, Rebecca J. G. Drake, Jesus Gomez-Escudero, Frances M. Richards, Celine Weller, Christof Dormann, Ya-Ming Meng, Peter B. Vermeulen, Dieter Saur, Victoria Sanz-Moreno, Ping-Pui Wong, Cyrill Geraud, Pedro R. Cutillas, Kairbaan Hodivala-Dilke
Summary: This study reveals that endothelial cell focal adhesion kinase (FAK) plays a role in regulating pancreatic ductal adenocarcinoma (PDAC) metastasis and impacting the outcome of gemcitabine treatment. The findings suggest the potential clinical utility of combinatorial endothelial cell FAK targeting with gemcitabine in controlling metastasis in PDAC patients.
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.
Article
Biochemistry & Molecular Biology
K. E. Richards, A. E. Zeleniak, M. L. Fishel, J. Wu, L. E. Littlepage, R. Hill
Article
Oncology
Ann E. Zeleniak, Wei Huang, Mary K. Brinkman, Melissa L. Fishel, Reginald Hill
Article
Oncology
Ann E. Zeleniak, Wei Huang, Melissa L. Fishel, Reginald Hill
Article
Chemistry, Analytical
David A. Rusak, Ann E. Zeleniak, Jillian L. Obuhosky, Scott M. Holdren, Craig A. Noldy
Article
Biochemical Research Methods
Ann Zeleniak, Connor Wiegand, Wen Liu, Catherine McCormick, K. Ravikumar, Amir Alavi, Haonan Guan, Suzanne Bertera, Robert Lakomy, Asako Tajima, Henry Cohen, Stephanie Wong, Lame Balikani, Benjamin Mizerak, Ziv Bar-Joseph, Massimo Trucco, Ipsita Banerjee, Yong Fan
Summary: This study successfully engineered human thymus organoids that can support the de novo generation of functional human T cells, exhibiting cellular and humoral immune functions in mice. This finding could enhance the efficiency of studying T cell-mediated immune disorders and drug discovery.