Review
Health Care Sciences & Services
Darren Cowzer, Mohammed Zameer, Michael Conroy, Walter Kolch, Austin G. Duffy
Summary: This article reviews therapeutic innovations targeting RAS signaling in pancreatic cancer from a clinical perspective. Despite the strong resistance of pancreatic cancer to treatment, new approaches such as inhibiting mutated KRAS, KRAS activators, and effectors show promise in breaking this therapeutic deadlock.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Asif Halimi, Giorgio Gabarrini, Michal Jacek Sobkowiak, Zeeshan Ateeb, Haleh Davanian, Rogier Aaron Gaiser, Urban Arnelo, Roberto Valente, Alicia Y. W. Wong, Carlos Fernandez Moro, Marco Del Chiaro, Volkan Ozenci, Margaret Sallberg Chen
Summary: The study reveals a potential link between pancreatic cystic lesions and cancer, with cultivated bacteria demonstrating pathogenic properties such as intracellular survival capability, cell death induction, and causing DNA double-strand breaks in surviving cells.
Article
Medicine, General & Internal
J. H. Strickler, H. Satake, T. J. George, R. Yaeger, A. Hollebecque, I Garrido-Laguna, M. Schuler, T. F. Burns, A. L. Coveler, G. S. Falchook, M. Vincent, Y. Sunakawa, L. Dahan, D. Bajor, S-Y Rha, C. Lemech, D. Juric, M. Rehn, G. Ngarmchamnanrith, P. Jafarinasabian, Q. Tran, D. S. Hong
Summary: This study evaluated the safety and efficacy of sotorasib in patients with KRAS p.G12C-mutated pancreatic cancer who had previously received treatment. The results showed that sotorasib demonstrated anticancer activity and had an acceptable safety profile in these patients.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Osamu Araki, Motoyuki Tsuda, Mayuki Omatsu, Mio Namikawa, Makoto Sono, Yuichi Fukunaga, Tomonori Masuda, Takaaki Yoshikawa, Munemasa Nagao, Satoshi Ogawa, Kenji Masuo, Norihiro Goto, Yu Muta, Yukiko Hiramatsu, Takahisa Maruno, Yuki Nakanishi, Sho Koyasu, Toshihiko Masui, Etsuro Hatano, Dieter Saur, Akihisa Fukuda, Hiroshi Seno
Summary: The chromatin remodeler Brg1 plays a critical role in the survival, growth, and metastasis of pancreatic ductal adenocarcinoma (PDAC) cells. Brg1 regulates the hypoxia pathway, which is important for maintaining the stem-like properties of PDAC cells and promoting their metastasis. This study suggests that Brg1 could be a potential therapeutic target for PDAC.
Editorial Material
Medicine, General & Internal
Cornelis J. M. Melief
Summary: Pancreatic ductal adenocarcinoma is the deadliest of all common cancers. The study reported remarkable deep and durable tumor shrinkage in a heavily pretreated patient who received an infusion of autologous T cells transduced.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemical Research Methods
Ann Morgell, Julie A. Reisz, Zeeshan Ateeb, Haleh Davanian, Susanne E. Reinsbach, Asif Halimi, Rogier Gaiser, Roberto Valente, Urban Arnelo, Marco Del Chiaro, Margaret Sallberg Chen, Angelo D'Alessandro
Summary: Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a low 5-year survival rate. Lack of reliable tools for early diagnosis complicates its management. Research has identified novel metabolic markers that can help determine the progression of pancreatic cysts and pancreatic cancer. These findings suggest a potential role of bacterial infections in the development and severity of pancreatic cancer, similar to other cancers like Helicobacter pylori and gastric cancer.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Oncology
Viola Hedrich, Kristina Breitenecker, Gregor Ortmayr, Franziska Pupp, Heidemarie Huber, Doris Chen, Sarthak Sahoo, Mohit Kumar Jolly, Wolfgang Mikulits
Summary: This study identified PRAME as a target gene of the Gas6/Axl signaling pathway in hepatocellular carcinoma. PRAME promotes dedifferentiation, epithelial-to-mesenchymal transition, and invasion in liver cancer cells. The expression of PRAME is associated with an unfavorable prognosis in HCC patients.
Review
Oncology
Yuta Adachi, Ryo Kimura, Kentaro Hirade, Hiromichi Ebi
Summary: Mutant KRAS-driven tumor cells can become independent of mutant KRAS by activating alternative pathways, leading to a mesenchymal phenotype and potential metastasis. YAP and/or RSK-mTOR pathway activation, along with mutations in LKB1, KEAP1, and/or NRF2, are linked to mutant KRAS autonomy. Understanding KRAS dependency is crucial for selecting patients for mutant-specific inhibitors, while investigating mechanisms of KRAS autonomy is important for developing optimal treatment strategies for KRAS-independent tumors.
Article
Endocrinology & Metabolism
Z. Gong, L. Xue, A. C. Vlantis, C. A. van Hasselt, J. Y. K. Chan, J. Fang, R. Wang, Y. Yang, D. Li, X. Zeng, M. C. F. Tong, G. G. Chen
Summary: This study demonstrated that Nrf2 plays a critical role in KRAS-mediated dedifferentiation of thyroid cancer, and the Nrf2 inhibitor Brusatol effectively counteracts the proliferative and invasive abilities induced by KRAS.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
John Fadul, Teresa Zulueta-Coarasa, Gloria M. Slattum, Nadja M. Redd, Mauricio Franco Jin, Michael J. Redd, Stephan Daetwyler, Danielle Hedeen, Jan Huisken, Jody Rosenblatt
Summary: The study demonstrates that KRas transformation alone causes cell invasion and partial dedifferentiation independently of mass formation. The invading cells use basal cell extrusion for invasion, and only invading KRas(V12) cells deficient in p53 survive and form internal masses.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lena Wiedmann, Francesca De Angelis Rigotti, Nuria Vaquero-Siguero, Elisa Donato, Elisa Espinet, Iris Moll, Elisenda Alsina-Sanchis, Hanibal Bohnenberger, Elena Fernandez-Florido, Ronja Muelfarth, Margherita Vacca, Jennifer Gerwing, Lena-Christin Conradi, Philipp Stroebel, Andreas Trumpp, Carolin Mogler, Andreas Fischer, Juan Rodriguez-Vita
Summary: The presence of peritoneal metastasis in pancreatic cancers is associated with poor prognosis. The authors found that HAPLN1 promotes tumor cell plasticity and pro-tumoral immune microenvironment to facilitate peritoneal dissemination in pancreatic cancers.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Lukas Krauss, Bettina C. Urban, Sieglinde Hastreiter, Carolin Schneider, Patrick Wenzel, Zonera Hassan, Matthias Wirth, Katharina Lankes, Andrea Terrasi, Christine Klement, Filippo M. Cernilogar, Rupert Oellinger, Niklas de Andrade Kraetzig, Thomas Engleitner, Roland M. Schmid, Katja Steiger, Roland Rad, Oliver H. Kraemer, Maximilian Reichert, Gunnar Schotta, Dieter Saur, Guenter Schneider
Summary: The mortality of patients with pancreatic ductal adenocarcinoma (PDAC) is strongly associated with metastasis, and transcriptional and epigenetic rewiring can contribute to the metastatic process. This study shows that HDAC2 plays a crucial role in undifferentiated PDAC by controlling cell cycle and metastasis. HDAC2 maintains the metastatic program by controlling the expression of several prosurvival receptor tyrosine kinases connected to mesenchymal PDAC, and impairs the tumor-suppressive arm of the TGFI3 pathway.
Article
Gastroenterology & Hepatology
Eileen C. Donovan, Laura R. Prakash, Yi-Ju Chiang, Morgan L. Bruno, Jessica E. Maxwell, Naruhiko Ikoma, Ching-Wei D. Tzeng, Matthew H. G. Katz, Jeffrey E. Lee, Michael P. Kim
Summary: This study compared the rates of postoperative complications in patients undergoing pancreatectomies for mucinous pancreatic cysts (MCs) or pancreatic ductal adenocarcinoma (PDAC). The results showed that the overall major 90-day postoperative complications were similar between MC and PDAC patients undergoing pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). The most common complications were postoperative pancreatic fistula (POPF), abscess, and postoperative bleeding. The incidence of 90-day ISGPS Grade B/C POPF was higher in MC patients undergoing PD but not DP. There were no significant differences in operative time or length of stay between MCs and PDAC cohorts.
JOURNAL OF GASTROINTESTINAL SURGERY
(2023)
Article
Immunology
Austin M. Eckhoff, Michael C. Brown, Karenia Landa, Ibtehaj Naqvi, Eda K. Holl, David Boczkowski, Ashley Fletcher, Kristen E. Rhodin, Minh Huy Giang, Bruce Sullenger, Georgia M. Beasley, Peter J. Allen, Smita K. Nair
Summary: This study found that monocytes in the periphery and tumor microenvironment of patients with intraductal papillary mucinous neoplasm (IPMN) and pancreatic adenocarcinoma (PDAC) undergo functional changes and are associated with immunosuppression and immune evasion. Furthermore, the study also revealed that TLR activation is positively correlated with disease progression from IPMN to PDAC. These findings suggest that innate immune reprogramming occurs as IPMNs progress to invasive disease, partly mediated by soluble mediators in sera.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Engineering, Biomedical
Ri Huang, Hong Du, Liang Cheng, Peizhuo Zhang, Fenghua Meng, Zhiyuan Zhong
Summary: In this study, cRGD peptide-modified bioresponsive chimaeric polymersomes (cRGD-BCP) were used for efficient delivery of siKRAS to PANC-1 tumor cells, resulting in potent silencing of KRAS G12D mRNA and effective suppression of pancreatic cancer tumor growth in mice. The density of cRGD greatly impacted the uptake and silencing efficiency of cRGD-BCP-siKRAS. cRGD-BCP-siKRAS significantly enhanced the uptake of siKRAS in PANC-1 tumor and achieved remarkable tumor inhibition and survival benefits.
ACTA BIOMATERIALIA
(2023)