Article
Gastroenterology & Hepatology
Ivana Peran, Sivanesan Dakshanamurthy, Matthew D. McCoy, Anastasia Mavropoulos, Bedilu Allo, Aimy Sebastian, Nicholas R. Hum, Sara C. Sprague, Kelly A. Martin, Michael J. Pishvaian, Eveline E. Vietsch, Anton Wellstein, Michael B. Atkins, Louis M. Weiner, Andrew A. Quong, Gabriela G. Loots, Stephen S. Yoo, Shahin Assefnia, Stephen W. Byers
Summary: The study showed that CDH11, expressed by cancer-associated fibroblasts in the pancreatic tumor stroma, plays a critical role in promoting tumor growth and immunosuppression. Knockout or inhibition of CDH11 reduced pancreatic tumor growth, increased response to gemcitabine, and significantly extended survival of mice. Thus, CDH11 may be a potential therapeutic target for pancreatic cancer.
Article
Oncology
Mara H. Sherman, Marina Pasca di Magliano
Summary: Cancer-associated fibroblasts (CAFs) are abundant in pancreatic ductal adenocarcinoma (PDAC) and have complex functions, including regulating the extracellular matrix, supporting cancer cell growth, and suppressing immune responses. Understanding the heterogeneity of CAFs and their functional roles is crucial for developing effective therapeutic strategies for PDAC.
ANNUAL REVIEW OF CANCER BIOLOGY
(2023)
Review
Cell Biology
Tianyi Zhang, Yanxian Ren, Pengfei Yang, Jufang Wang, Heng Zhou
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with a high deposition of extracellular matrix (ECM) and poor prognosis. ECM proteins derived from tumor cells reduce the effectiveness of conventional cancer treatment and contribute to tumor progression and metastasis. Cancer-associated fibroblasts (CAFs) in the ECM are promising targets for novel anti-tumor interventions.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Taija Korpela, Ari Ristimaki, Marianne Udd, Tiina Vuorela, Harri Mustonen, Caj Haglund, Leena Kylanpaa, Hanna Seppanen
Summary: This study investigated the potential role of histological chronic pancreatitis findings and chronic inflammation in surgical pancreatic ductal adenocarcinoma (PDAC) specimens on disease-specific survival (DSS). The results suggest that more severe fibrosis, acinar atrophy, and chronic inflammation in the pancreatic stroma were associated with worse DSS outcomes for PDAC patients.
Review
Biochemistry & Molecular Biology
Natalie Geyer, Marco Gerling
Summary: The Hedgehog (Hh) signaling pathway plays a diverse role in colorectal cancer, with the canonical pathway acting as a tumor suppressor while non-canonical activation may promote tumor growth in certain cells. Researchers suggest that a more detailed understanding of the Hh signaling pathway could lead to the development of new cancer therapies in the future, despite discouraging results from previous clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Menekse Ermis, Natashya Falcone, Natan Roberto De Barros, Marvin Mecwan, Reihaneh Haghniaz, Auveen Choroomi, Mahsa Monirizad, Yeji Lee, Jihyeon Song, Hyun-Jong Cho, Yangzhi Zhu, Heemin Kang, Mehmet R. Dokmeci, Ali Khademhosseini, Junmin Lee, Han -Jun Kim
Summary: The tumor microenvironment, particularly the matrix component, plays a crucial role in the progression and therapeutic responsiveness of PDAC. By engineering hyaluronic acid and gelatin-based hydrogels to mimic desmoplastic matrices, a multicellular pancreatic tumor model is developed that allows for a better understanding and monitoring of PDAC progression, with potential applications in personalized medicine and drug testing.
BIOACTIVE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Vida Karimnia, M. Elizabeth Stanley, Christian T. Fitzgerald, Imran Rizvi, Frank J. Slack, Jonathan P. Celli
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with obstructed drug delivery and tumor-promoting fibrous stroma. Photodynamic therapy (PDT) has been shown to be feasible and effective for PDAC. This study investigates the ability of photodynamic stromal depletion (PSD) to enhance RNA nanomedicine delivery, and finds that PSD improves the transport of therapeutic nanoparticles and enhances the tumor response to treatment. These findings suggest that PSD could be developed to enhance the delivery of other cancer therapeutics.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2023)
Review
Immunology
Sophie Liot, Jonathan Balas, Alexandre Aubert, Laura Prigent, Perrine Mercier-Gouy, Bernard Verrier, Philippe Bertolino, Ana Hennino, Ulrich Valcourt, Elise Lambert
Summary: Pancreatic cancer, especially PDAC, has a poor prognosis with low survival rates, mainly due to its dense stroma deposition and immune suppression in the TME. Research on TME composition may lead to new therapeutic targets for better treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Gastroenterology & Hepatology
Hossein Jahedi, Anassuya Ramachandran, John Windsor, Nicholas Knowlton, Cherie Blenkiron, Cristin G. G. Print
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy known for its poor prognosis. The dense desmoplastic stroma and abundant hyaluronic acid (HA) play crucial roles in PDAC. However, despite strong evidence, a HA-targeting drug failed in clinical trials, emphasizing the need for a better understanding of HA biology in PDAC.
Review
Oncology
Yang Wu, Chun Zhang, Kuirong Jiang, Jens Werner, Alexandr V. Bazhin, Jan G. D'Haese
Summary: PDAC progression is influenced by PSCs, which through interactions with PCCs and other stroma cells, establish a tumor microenvironment that promotes tumor growth, metastasis, and chemoresistance. Targeting stroma has emerged as a promising strategy for PDAC therapy, with several novel strategies proposed to intervene in this complex crosstalk.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Maria Joao Amaral, Mariana Amaral, Joao Freitas, Rui Caetano Oliveira, Marco Serodio, Maria Augusta Cipriano, Jose Guilherme Tralhao
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, which accounts for 80% of its volume. The amount of stroma may affect prognosis, but its specific impact remains uncertain. This study aimed to investigate prognostic factors for PDAC patients undergoing surgery, including the impact of tumor stroma area (TSA). A retrospective study was conducted with PDAC patients who underwent surgical resection. TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa were identified as independent risk factors for mortality in PDAC patients undergoing surgery. Regarding TSA, a larger TSA seemed to be associated with longer overall survival (OS) for all stages. In stage II patients, a larger TSA was significantly associated with R0 resection, while in stage III patients, a larger TSA was significantly associated with a lower histological grade, higher preoperative AP levels, and lower preoperative AST levels. Patients with PDAC undergoing surgical resection and having preoperative CA19.9 > 500 U/L and AST >= 100 U/L had a higher risk of recurrence, although tumor stroma may have a protective effect in these patients.
Article
Oncology
Jiahong Jiang, Yaping Xu, Lianpeng Chang, Guoqing Ru, Xuefeng Xia, Ling Yang, Xin Yi, Zheling Chen, Dong-Sheng Huang, Liu Yang
Summary: This study revealed the presence of driver gene mutations in PDAC stroma, indicating that the genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and may help guide a more precise treatment paradigm in therapeutic options.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Jordi Alcaraz, Rafael Ikemori, Alejandro Llorente, Natalia Diaz-Valdivia, Noemi Reguart, Miguel Vizoso
Summary: Lung cancer is the leading cause of cancer-related death worldwide, with the stroma of lung cancer and other solid tumors being rich in tumor-associated fibroblasts (TAFs) exhibiting an activated/myofibroblast-like phenotype. Growing evidence suggests that TAFs support key steps of tumor progression and are epigenetically reprogrammed compared to healthy fibroblasts. The mechanisms underlying this reprogramming involve interactions with cancer cells, pro-fibrotic cytokines, extracellular matrix stiffness, smoking particles, and other environmental cues, leading to DNA hypomethylation and selective transcriptional repression in lung TAFs.
Review
Oncology
Kay Myo K. Min, Charlie B. Ffrench, Claire F. Jessup, Mia Shepherdson, Savio George Barreto, Claudine S. Bonder
Summary: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor, with a 5-year survival rate of less than 9%. PDAC tumors have a dense fibrotic barrier that hinders drug penetration and provides a favorable environment for cancer cell growth. This review discusses the role of the tumor microenvironment (TME) in PDAC development, current treatments, and clinical trials targeting TME components.
Article
Oncology
Tomohiko Shinkawa, Kenoki Ohuchida, Yuki Mochida, Kukiko Sakihama, Chika Iwamoto, Toshiya Abe, Noboru Ideno, Yusuke Mizuuchi, Koji Shindo, Naoki Ikenaga, Taiki Moriyama, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
Summary: The presence of abundant stroma in pancreatic ductal adenocarcinoma (PDAC) can define the PDAC phenotype and induce distinct therapeutic responses. Cancer-associated fibroblasts (CAFs) maintain the differentiated PDAC phenotype through secreting niche factors and induce different drug responses.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Kristin Stendahl, Syed M. Gilani, Olca Basturk, Pei Hui, Carlie Sigel, Guoping Cai
Summary: Our study analyzed cytomorphologic and molecular features of intraductal papillary neoplasm of the bile duct (IPNB) cases. The cytomorphologic features of IPNB included papillary/complex papillary architecture, columnar cells with vacuolated cytoplasm, enlarged nuclei, and fine granular chromatin. Most cases had adenocarcinoma or high-grade dysplasia, and KRAS mutations were found in a significant number of cases, which may have diagnostic and therapeutic implications.
CANCER CYTOPATHOLOGY
(2023)
Article
Pathology
Claudio Luchini, Paola Mattiolo, Olca Basturk, Andrea Mafficini, Kerem Ozcan, Rita T. Lawlor, Seung-Mo Hong, Lodewijk A. Brosens, Giovanni Marchegiani, Antonio Pea, Erminia Manfrin, Giuseppe Sciacca, Federica Zampieri, Rita Polati, Riccardo De Robertis, Michele Milella, Mirko D'Onofrio, Giuseppe Malleo, Roberto Salvia, Volkan Adsay, Aldo Scarpa
Summary: Acinar cystic transformation (ACT) of the pancreas is a poorly understood and rare entity among pancreatic cystic lesions. This study aims to clarify its real nature by describing the clinicopathological features and molecular profile of a cohort of 25 patients with pancreatic ACT. The findings suggest that ACT is a benign entity potentially arising from diverse conditions/backgrounds, but the presence of driver mutations raises the possibility of long-term surveillance for these patients.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Oncology
Diana Mandelker, Antonio Marra, Nikita Mehta, Pier Selenica, Zarina Yelskaya, Ciyu Yang, Joshua Somar, Miika Mehine, Maksym Misyura, Olca Basturk, Alicia Latham, Maria Carlo, Michael Walsh, Zsofia K. Stadler, Kenneth Offit, Chaitanya Bandlamudi, Meera Hameed, Ping Chi, Jorge S. Reis-Filho, Ozge Ceyhan-Birsoy
Summary: Traditional genetic testing for GISTs focuses on patients with syndromic features. However, expanded genetic testing revealed that 69% of KIT/PDGFRA-wildtype GIST patients had pathogenic/likely pathogenic variants in GIST-associated genes, even without a history of syndromic features. Additionally, somatic variants identified in tumor-only sequencing of GISTs were found to be largely germline in origin.
NPJ PRECISION ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Luis A. Rojas, Zachary Sethna, Kevin C. Soares, Cristina Olcese, Nan Pang, Erin Patterson, Jayon Lihm, Nicholas Ceglia, Pablo Guasp, Alexander Chu, Rebecca Yu, Adrienne Kaya Chandra, Theresa Waters, Jennifer Ruan, Masataka Amisaki, Abderezak Zebboudj, Zagaa Odgerel, George Payne, Evelyna Derhovanessian, Felicitas Mueller, Ina Rhee, Mahesh Yadav, Anton Dobrin, Michel Sadelain, Marta Luksza, Noah Cohen, Laura Tang, Olca Basturk, Mithat Goenen, Seth Katz, Richard Kinh Do, Andrew S. Epstein, Parisa Momtaz, Wungki Park, Ryan Sugarman, Anna M. Varghese, Elizabeth Won, Avni Desai, Alice C. Wei, Michael I. D'Angelica, T. Peter Kingham, Ira Mellman, Taha Merghoub, Jedd D. Wolchok, Ugur Sahin, Oezlem Tuereci, Benjamin D. Greenbaum, William R. Jarnagin, Jeffrey Drebin, Eileen M. O'Reilly, Vinod P. Balachandran
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a high mortality rate, but it can be targeted using mutation-derived T cell neoantigens as vaccines. In this phase I trial, researchers synthesized individualized mRNA neoantigen vaccines from PDAC tumors and administered them to patients along with atezolizumab, autogene cevumeran, and mFOLFIRINOX chemotherapy. The results showed that the autogene cevumeran vaccine induced neoantigen-specific T cells in patients, and those with vaccine-expanded T cells had a longer recurrence-free survival.
Review
Gastroenterology & Hepatology
Laura D. Wood, N. Volkan Adsay, Olca Basturk, Lodewijk A. A. Brosens, Noriyoshi Fukushima, Seung-Mo Hong, Sung-Joo Kim, Jae W. Lee, Claudio Luchini, Michael Noe, Martha B. Pitman, Aldo Scarpa, Aatur D. Singhi, Mariko Tanaka, Toru Furukawa
Summary: This review presents updated perspectives on key issues in the examination of pathological specimens in patients with intraductal papillary mucinous neoplasms (IPMN), providing a foundation for data-driven approaches.
Meeting Abstract
Medicine, Research & Experimental
David Adsay, Rohat Esmer, Ozgur Eren, Ayse Armutlu, Orhun Taskin, Berke Cesur, Ulkem Kasapoglu, Soner Koc, Nuray Tezcan, Berk Kaan Aktas, Ibrahim Kulac, Yersu Kapran, Olca Basturk, Cigdem Gunduz-Demir, Burcu Saka
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Mustafa Erdem Arslan, Kerem Ozcan, Hulya Sahin Ozkan, Daniela Allende, Funda Yilmaz, Rondell Graham, Raul Gonzalez, Jiaqi Shi, N. Volkan Adsay, Christopher Fletcher, David Klimstra, Olca Basturk
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Emre Bozkurt, Rohat Esmer, Burcu Saka, Ozgur Eren, Pelin Bagci, Serdar Balci, Ayse Armutlu, Cenk Sokmensuer, Yue Xue, Burcin Pehlivanoglu, Michelle Reid, Shishir Maithel, David Kooby, Juan Sarmiento, Orhun Taskin, Yersu Kapran, Bengi Gurses, Gurkan Tellioglu, Orhan Bilge, Olca Basturk, N. Volkan Adsay
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Esma Ersoy, Aslihan Yavas, Keith Sigel, Nicolas Lecomte, Xianlu Peng, Jen Jen Yeh, Olca Basturk, Carlie Sigel
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Rohat Esmer, Zeynep Tarcan, Kadriye Akar, Pelin Bagci, Nobuyuki Ohike, Keetaek Jang, Emine Bozkurtlar, Burcu Saka, Ayse Armutlu, Orhun Taskin, Serdar Balci, Grace Kim, Yue Xue, Shishir Maithel, Juan Sarmiento, Bahar Memis, Jeanette Cheng, Michelle Reid, Olca Basturk, N. Volkan Adsay
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Kerem Ozcan, Hulya Sahin Ozkan, Pietro Antonini, Claudio Luchini, Burcu Saka, Yue Xue, Michelle Reid, Aldo Scarpa, N. Volkan Adsay, Olca Basturk
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Kerem Ozcan, Hulya Sahin Ozkan, Laura Tang, Bahar Memis, Grace Kim, Sui Zee, Guoli Chen, Zhaohai Yang, David Klimstra, N. Volkan Adsay, Olca Basturk
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Hulya Sahin Ozkan, Kerem Ozcan, Bahar Memis, Burcin Pehlivanoglu, Gokce Askan, Pelin Bagci, N. Volkan Adsay, David Klimstra, Olca Basturk
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Zeynep Tarcan, Rohat Esmer, Kadriye Akar, Pelin Bagci, Emine Bozkurtlar, Burcu Saka, Ayse Armutlu, Hulya Sahin Ozkan, Kerem Ozcan, Orhun Taskin, Yersu Kapran, Makbule Aydin Mericoz, Serdar Balci, Serpil Yilmaz, Duygu Cengiz, Bengi Gurses, Emrah Alper, Gurkan Tellioglu, Emre Bozkurt, Orhan Bilge, Olca Basturk, N. Volkan Adsay
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Nuray Tezcan, Duygu Cengiz, Rohat Esmer, Berk Kaan Aktas, Ayse Armutlu, Burcu Saka, Ozgur Kurt, Orhun Taskin, Yersu Kapran, Hatice Goksu Kayim, Afak Durur Karakaya, Emre Bozkurt, Gurkan Tellioglu, Orhan Bilge, Emrah Alper, Olca Basturk, Bengi Gurses, N. Volkan Adsay
LABORATORY INVESTIGATION
(2023)
