Review
Gastroenterology & Hepatology
Benno Traub, Aileen Roth, Marko Kornmann, Uwe Knippschild, Joachim Bischof
Summary: Pancreatic cancer is a devastating disease with poor survival rates, prompting the need for new therapeutic approaches. Protein kinases play crucial roles in development and pathogenesis, making them potential targets for precision medicine in patients with deregulated kinase pathways.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Cell Biology
Arian Ansardamavandi, Mehrdad Nikfarjam, Hong He
Summary: Angiogenesis is associated with solid tumors, but anti-angiogenesis drugs can make tumors more aggressive and do not improve overall survival rate in pancreatic cancer. Targeting p21-activated kinases (PAKs) inhibits cancer cell growth, enhances anti-tumor immunity, and improves chemotherapy and Car-T immunotherapy.
Article
Biotechnology & Applied Microbiology
Yin-Hao Shi, Qiong-Cong Xu, Ying-Qin Zhu, Zhi-De Liu, Guang-Yin Zhao, Qi Liu, Xi-Yu Wang, Jie-Qin Wang, Xiang Xu, Qiao Su, Jia-Ming Lai, Chen-Song Huang, Xiao-Yu Yin
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with poor prognosis. Gemcitabine-based chemotherapy is one of the main treatment modalities, but gemcitabine resistance frequently occurs. Platelet-derived growth factor C (PDGFC) is abnormally highly expressed in gemcitabine-resistant PDAC. Silencing PDGFC expression enhances the therapeutic effect of gemcitabine on PDAC. PDGFC promotes gemcitabine resistance by activating the PDGFR-PI3K-AKT signaling pathway.
Article
Oncology
Yi Ma, Mehrdad Nikfarjam, Hong He
Summary: Pancreatic Ductal Adenocarcinoma (PDA) is a deadly cancer with KRAS mutation as a common oncogene. P21-activated kinases (PAKs) are downstream mediators of KRAS and play a role in PDA tumorigenesis. Inhibiting PAK reduces cancer cell viability and sensitizes them to chemotherapy. PAK inhibition also increases cancer immunogenicity in melanoma, glioblastoma, and PDA. Autophagy is important in PDA immune evasion and there is a connection between PAK and cancer cell autophagy.
Article
Multidisciplinary Sciences
Daniel R. Principe, Alexandre F. Aissa, Sandeep Kumar, Thao N. D. Pham, Patrick W. Underwood, Rakesh Nair, Rong Ke, Basabi Rana, Jose G. Trevino, Hidayatullah G. Munshi, Elizaveta Benevolenskaya, Ajay Rana
Summary: There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). In this study, researchers identified a subset of gemcitabine-resistant tumor cells enriched for calcium/calmodulin signaling. Inhibition of calcium-dependent calmodulin activation led to the loss of drug-resistant phenotypes, and calcium chelation or depletion impaired ERK activation and restored therapeutic responses to gemcitabine. Calcium channel blockers also enhanced therapeutic responses to gemcitabine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Mohankumar Amirthalingam, Sundararaj Palanisamy, Shinkichi Tawata
Summary: PAKs are a group of kinases involved in a wide range of cellular functions and have been implicated as not only oncogenic but also aging kinases. Targeting PAKs could be a potential strategy for cancer therapy development with minimal side effects and promoting healthy longevity.
AGEING RESEARCH REVIEWS
(2021)
Review
Cell Biology
Kaifan Zhang, Yan Wang, Tianda Fan, Cheng Zeng, Zhong Sheng Sun
Summary: PAKs are main effectors of the Rho GTPases Cdc42 and Rac, linking complex cytoskeletal networks to neural activity. They play a crucial role in neuronal development, dendritic spine plasticity, and are implicated in neurodevelopmental and neurodegenerative disorders. Comprehensive understanding of PAKs' role in neural cytoskeletal remodeling can enhance our knowledge of neurological diseases and potentially provide therapeutic targets.
Review
Cell Biology
Alica K. Beutel, Christopher J. Halbrook
Summary: Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer-related deaths worldwide and its treatment is challenging due to a lack of durable responses to standard-of-care chemotherapies. Gemcitabine, a cornerstone in PDA treatment, faces resistance mechanisms that have not yet been overcome in patient care.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Oncology
Xiaodong Li, Feng Li
Summary: Gastrointestinal tumors are the most common tumors with high mortality rate worldwide. PAK, a serine/threonine kinase, plays a crucial role in tumor phenotype by influencing cell proliferation, survival, motility, tumor cell plasticity, and the tumor microenvironment. Understanding the features and signaling pathways of PAK in cells, especially its role in gastrointestinal tumors, can provide a theoretical basis for future research on PAK and potential therapeutic targets.
Article
Cell Biology
Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Summary: Research has shown that ZWINT is overexpressed in pancreatic cancer and promotes tumor growth by activating the p53/p21 signaling pathway. ZWINT interacts with p53 and promotes its ubiquitination and degradation, thus facilitating proliferation in pancreatic cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Dianyun Ren, Yan Sun, Dan Li, Heshui Wu, Xin Jin
Summary: PTEN is a dual lipid and protein phosphatase that plays a crucial role in pancreatic cancer. USP22 has been identified as a novel modifying enzyme of PTEN, enhancing p21 expression and inhibiting cancer progression. Moreover, ANKHD1 and MDM2 could be potential therapeutic targets for pancreatic cancer treatment.
MOLECULAR ONCOLOGY
(2022)
Article
Engineering, Environmental
Xiao Fu, Xiaoxuan Zhang, Danqing Huang, Liang Mao, Yudong Qiu, Yuanjin Zhao
Summary: Inspired by the structures of octopus tentacles, researchers have developed a novel adhesive microneedle patch with gemcitabine encapsulation for the treatment of pancreatic cancer. The patch, made of gelatin methacryloyl, demonstrates good biocompatibility, flexibility, and drug loading efficiency. It can adhere to the irregular surfaces of tumors and efficiently release gemcitabine to penetrate tumor tissues, showing promising anti-tumor efficacy in vitro and in a mouse model.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Multidisciplinary Sciences
Chen Chen, Binfeng Wu, Mingge Wang, Jinghua Chen, Zhaohui Huang, Jin-Song Shi
Summary: Our findings suggest that GABRP may serve as a downstream target of CD44s to diminish gemcitabine resistance in pancreatic cancer, and both CD44s and GABRP molecules have the potential to become prognostic biomarkers for PDAC patients with gemcitabine resistance.
Article
Pharmacology & Pharmacy
Tianli Zhang, Mengmeng Liu, Qing Liu, Gary Guishan Xiao
Summary: Wogonin can enhance the sensitivity of pancreatic cancer cells to gemcitabine chemotherapy, possibly by promoting apoptosis through inhibiting the Akt signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jingjing Yao, Min Huang, Qinghong Shen, Ming Ding, Shaofang Yu, Yajuan Guo, Yuefang Lin, Yaqiu Zheng, Wenbo Chen, Wenxin Yan, Zhongqiu Liu, Dawei Wang, Ming Hu, Linlin Lu
Summary: Pancreatic cancer has a low overall survival rate and is often resistant to the first-line drug, Gemcitabine. This study found that c-Myc and PD-L1 were highly expressed in pancreatic tumors and dFdC-resistant cells. Moreover, the combination of dFdC and c-Myc inhibitors enhanced drug sensitivity, while overexpression of c-Myc reduced sensitivity. Additionally, ARTS was shown to reverse dFdC resistance in vitro and suppress pancreatic cancer in vivo.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarah A. Long, Shan Huang, Anusha Kambala, Ling Ren, Jennifer Wilson, Michael Goetz, Xiaojiang Hao, Xiaosheng Yang, Ekaterina I. Goncharova, Libin Jia, Amy LeBlanc, Chand Khanna, Curtis J. Henrich, John A. Beutler
Summary: A high-throughput screening method was developed to identify compounds selectively inhibiting the in vitro growth of highly metastatic osteosarcoma cells, leading to the discovery of lovastatin and the limonoid toosendanin. Cerivastatin was identified as a particularly potent and selective agent, inducing apoptosis in metastatic osteosarcoma cells. These statins and limonoids may present new opportunities for studying osteosarcoma metastasis.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Gastroenterology & Hepatology
Stephan B. Dreyer, Rosie Upstill-Goddard, Viola Paulus-Hock, Clara Paris, Eirini-Maria Lampraki, Eloise Dray, Bryan Serrels, Giuseppina Caligiuri, Selma Rebus, Dennis Plenker, Zachary Galluzzo, Holly Brunton, Richard Cunningham, Mathias Tesson, Craig Nourse, Ulla-Maja Bailey, Marc Jones, Kim Moran-Jones, Derek W. Wright, Fraser Duthie, Karin Oien, Lisa Evers, Colin J. McKay, Grant A. McGregor, Aditi Gulati, Rachel Brough, Ilirjana Bajrami, Stephan Pettitt, Michele L. Dziubinski, Juliana Candido, Frances Balkwill, Simon T. Barry, Robert Grutzmann, Lola Rahib, Amber Johns, Marina Pajic, Fieke E. M. Froeling, Phillip Beer, Elizabeth A. Musgrove, Gloria M. Petersen, Alan Ashworth, Margaret C. Frame, Howard C. Crawford, Diane M. Simeone, Chris Lord, Debabrata Mukhopadhyay, Christian Pilarsky, David A. Tuveson, Susanna L. Cooke, Nigel B. Jamieson, Jennifer P. Morton, Owen J. Sansom, Peter J. Bailey, Andrew Biankin, David K. Chang
Summary: DDR deficiency and replication stress are independent of each other, offering opportunities for therapy in DDR-proficient PC and after platinum therapy. Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes, and serve as a valuable model for studying novel therapeutic strategies targeting DDR and replication stress in PC.
Article
Radiology, Nuclear Medicine & Medical Imaging
Marlon Perera, Joseph Ischia, Damien Bolton, Arthur Shulkes, Graham S. Baldwin, Oneel Patel
Summary: The study found that zinc preconditioning can reduce oxidative stress in renal cells induced by contrast media, leading to increased cell survival.
CONTRAST MEDIA & MOLECULAR IMAGING
(2021)
Review
Oncology
Laura Castelletti, Dannel Yeo, Nico van Zandwijk, John E. J. Rasko
Summary: Malignant mesothelioma is a challenging tumor with limited treatment options. CAR-T cell therapy targeting the antigen mesothelin shows promise, but efficacy is currently modest. Overcoming the challenges posed by the MM tumor microenvironment and finding more effective treatment strategies will be the focus of future research.
BIOMARKER RESEARCH
(2021)
Article
Chemistry, Organic
Dongdong Wang, Wei Jiang, Chang-Kwon Kim, Heidi R. Bokesch, Girma M. Woldemichael, Berkley E. Gryder, John F. Shern, Jammed Khan, Barry R. O'Keefe, John A. Beutler, Kirk R. Gustafson
Summary: Neopetrothiazide (1) is a pentacyclic isoquinoline quinone isolated from a Neopetrosia sp. sponge. The structure elucidation was achieved through NMR experiments, revealing its unique thiazide-fused structural scaffold and 14 contiguous nonprotonated centers.
Article
Cell Biology
Patricia C. Cortelo, Daniel P. Demarque, Renata G. Dusi, Lorena C. Albernaz, Raimundo Braz-Filho, Ekaterina I. Goncharova, Heidi R. Bokesch, Kirk R. Gustafson, John A. Beutler, Laila S. Espindola
Summary: The study conducted high-throughput cytotoxicity screening on 702 extracts from 95 plant species in the Brazilian Cerrado biome, identifying 22 active extracts with significant cytotoxic activity against cancer cells. A molecular networking strategy annotated 27 compounds present in 17 active extracts, providing valuable chemical information for further studies on potential anticancer agents in plants.
Article
Surgery
Benjamin J. Privett, Marcos V. Perini, Laurence Weinberg, Michael A. Fink, Vijayaragavan Muralidharan, Eunice Lee, Graham Starkey, Robert Jones, Yi-Ju Lin, Mehrdad Nikfarjam
Summary: The study suggests that using polyethylene glycol and recombinant human albumin sealant in distal pancreatectomy can reduce the occurrence of postoperative pancreatic fistula. This method is associated with lower rates of clinically significant POPF and shorter hospital stays.
ANZ JOURNAL OF SURGERY
(2021)
Article
Plant Sciences
Fatma Tosun, Erdi C. Aytar, John A. Beutler, Jennifer A. Wilson, Mahmut Miski
Summary: Preliminary 2-day cancer cell screening assays showed strong cytotoxic activity in the dichloromethane extract of Heptaptera cilicica roots, resulting in the isolation of eleven sesquiterpene coumarin ethers with potent and selective cytotoxic activities. Revised spectroscopic data for 14'-acetoxybadrakemone and complete NMR spectroscopic assignments for colladonin and colladin were reported.
RECORDS OF NATURAL PRODUCTS
(2021)
Review
Oncology
Dannel Yeo, Laura Castelletti, Nico van Zandwijk, John E. J. Rasko
Summary: Mesothelioma is a deadly cancer with limited treatment options. Mesothelin is overexpressed in mesothelioma but not in normal cells, making it a potential biomarker and therapeutic target. Research on the diagnostic and therapeutic value of mesothelin in mesothelioma patients is ongoing to improve patient outcomes.
Review
Biochemistry & Molecular Biology
Dannel Yeo, Althea Bastian, Heidi Strauss, Payal Saxena, Peter Grimison, John E. J. Rasko
Summary: This review summarizes the data on the utility of CTCs in PDAC and discusses the molecular profiling and culture methods of CTCs. CTCs have the potential to be used in screening, early diagnosis, prognostic assessment, and personalized management of PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
P. J. Ross, H. S. Wasan, D. Croagh, M. Nikfarjam, N. Nguyen, M. Aghmesheh, A. M. Nagrial, D. Bartholomeusz, A. Hendlisz, T. Ajithkumar, C. Iwuji, N. E. Wilson, D. M. Turner, D. C. James, E. Young, M. T. Harris
Summary: This study suggests that combining P-32 microparticles with standard-of-care chemotherapy may have clinically relevant benefits for patients with unresectable locally advanced pancreatic cancer. The treatment has an acceptable safety profile and results in improved local disease control and overall survival.
Review
Oncology
Dannel Yeo, Caroline Giardina, Payal Saxena, John E. J. Rasko
Summary: Pancreatic cancer is a highly aggressive disease that is expected to become the second leading cause of cancer-related death worldwide. Current treatments for pancreatic cancer are limited, and cellular immunotherapy, particularly CAR T cell therapy, has shown limited efficacy. This review provides an overview of ongoing clinical studies and strategies to improve CAR T cell efficacy in pancreatic cancer.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Chemistry, Medicinal
David P. Stockdale, John A. Beutler, David F. Wiemer
Summary: The stilbene moiety is commonly found in natural products and compounds with this structure exhibit a wide range of biological activity. However, the cis/trans isomerization of stilbenes is a potential limitation for developing useful drugs. In this study, analogues of two bioactive stilbenes were synthesized, in which a 1,2,3-triazole ring replaced the stilbene double bond, aiming to address this drawback while preserving the biological activity. The new analogue showed strong anti-proliferative activity against 60 cell lines, which correlated well with the compound that inspired its synthesis.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Oncology
Krithika Murali, Tanya M. Dwarte, Mehrdad Nikfarjam, Katherine M. Tucker, Rhys B. Vaughan, Marios Efthymiou, Allison Collins, Allan D. Spigelman, Lucinda Salmon, Amber L. Johns, David B. Williams, Martin B. Delatycki, Thomas John, Alina Stoita
Summary: The Australian Pancreatic Cancer Screening Program offers endoscopic ultrasound surveillance for high-risk individuals requiring assessment by a Familial Cancer Service. The study found that 29.1% of the high-risk cohort had germline pathogenic variants associated with PDAC, with 10.4% of newly detected germline pathogenic variants among individuals who underwent genetic testing.
HEREDITARY CANCER IN CLINICAL PRACTICE
(2021)
Article
Biochemistry & Molecular Biology
Yang Yang, Nhi Huynh, Chelsea Dumesny, Kai Wang, Hong He, Mehrdad Nikfarjam
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.