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.
Editorial Material
Cell Biology
Jenny A. Rudnick, Jayanta Debnath
Summary: Growing evidence suggests that autophagy in the host stroma plays a crucial role in influencing the tumor microenvironment, particularly in promoting mammary tumor progression. Loss of fibroblast autophagy hinders the secretion of type 1 collagen, leading to an impairment in the development of a stiff tissue matrix conducive to mammary tumor growth. Therefore, targeting autophagy in stromal fibroblasts could be a potential strategy to inhibit the desmoplastic response required for cancer progression.
Review
Cell Biology
Min Kim, Changhu Lee, Jiyoung Park
Summary: Obesity is a global public health concern and a significant risk factor for metabolic diseases and various cancers. Fibro-inflammation and excessive extracellular matrix (ECM) production in adipose tissues play a crucial role in the pathogenesis of obesity. The ECM is a critical component of tissues, regulating cell survival, development, and tissue repair. ECM remodeling in adipose tissues affects the physical shape and biological function of adipose tissues, which in turn influences obesity-related cancer progression.
TRENDS IN CELL BIOLOGY
(2022)
Article
Biochemical Research Methods
Jungheun Hyun, Soyeong Jun, Hyeonseob Lim, Hyunjun Cho, Sung-Hwan You, Sang-Jun Ha, Jung-Joon Min, Duhee Bang
Summary: The study demonstrates that engineered Salmonella can serve as a carrier for neoantigen immunotherapy, showing promising efficacy in treating cancer in mice experiments.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Multidisciplinary Sciences
Candice R. Gurbatri, Nicholas Arpaia, Tal Danino
Summary: With the use of synthetic biology tools, researchers are repurposing bacteria as tumor-specific delivery systems, which can modulate the tumor microenvironment and enhance therapeutic efficacy and safety through their immunogenicity and local payload production.
Review
Oncology
Tiago M. A. Carvalho, Daria Di Molfetta, Maria Raffaella Greco, Tomas Koltai, Khalid O. Alfarouk, Stephan J. Reshkin, Rosa A. Cardone
Summary: PDAC has a poor prognosis due to the lack of early diagnosis, suitable biomarkers, and resistance to available therapies. The desmoplastic stroma in PDAC compromises treatments by reprogramming cellular metabolism, leading to impaired response to therapy. Understanding the mechanisms of PDAC resistance is crucial for improving patient outcomes.
Article
Oncology
Jay Natu, Ganji Purnachandra Nagaraju
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with high chemoresistance. Gemcitabine, one of the primary treatments for PDAC, has limited benefits due to interactions with the tumor microenvironment (TME). Preclinical models have shown that certain schedules of gemcitabine administration can modulate the TME without promoting resistance. Metronomic therapy is a promising strategy to overcome barriers in PDAC treatments.
Review
Gastroenterology & Hepatology
Thomas Lambin, Cyril Lafon, Robert Andrew Drainville, Mathieu Pioche, Frederic Prat
Summary: Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of death from cancer by 2030. The tumoral microenvironment (TME) of PDAC, characterized by fibrosis, hypo microvascular perfusion, and immunosuppression, is a major barrier to effective antitumoral treatment. Locoregional therapies, such as radiofrequency ablation and radiation therapy, hold promise for overcoming these barriers and improving clinical outcomes for PDAC patients.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Oncology
Matthew G. K. Benesch, Rongrong Wu, Gopal Menon, Kazuaki Takabe
Summary: The expression of beta integrins in PDAC is associated with the biological characteristics and clinical outcomes of tumors, but different integrins have different effects. ITGB1, 2, 5, and 6 are associated with TGF-beta, epithelial mesenchymal transition, inflammation, stemness, and angiogenesis pathways. High expression of ITGB1, 5, and 6 is associated with poor prognosis. ITGB2, 5, and 6 show similar characteristics to ITGB1, suggesting that future research should consider the complementary signaling profiles mediated by these integrins in PDAC therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Review
Oncology
Eileen Carpenter, Sarah Nelson, Filip Bednar, Clifford Cho, Hari Nathan, Vaibhav Sahai, Marina Pasca di Magliano, Timothy L. Frankel
Summary: This review explores the molecular components responsible for the immune-privileged state in pancreatic ductal adenocarcinoma (PDAC) and provides an overview of immunotherapeutic strategies for PDAC, including vaccine therapy, checkpoint blockade, myeloid-targeted therapy, and immune agonist therapy.
JOURNAL OF SURGICAL ONCOLOGY
(2021)
Article
Oncology
Gokce Askan, Ibrahim Halil Sahin, Joanne F. Chou, Aslihan Yavas, Marinela Capanu, Christine A. Iacobuzio-Donahue, Olca Basturk, Eileen M. O'Reilly
Summary: The study found that the expression of CD44 and ESA in PDAC patients is related to tumor stroma type, and tumor stroma may influence recurrence patterns, but there was no significant difference among subgroups in terms of RFS and OS.
Article
Multidisciplinary Sciences
Sherif G. Ahmed, Giulia Oliva, Manlin Shao, Xinhui Wang, John J. Mekalanos, Gary J. Brenner
Summary: This study evaluated the efficacy of Salmonella typhimurium as an immunotherapy for schwannomas. It was found that Salmonella typhimurium can control tumor growth and induce host immune responses. Intratumoral injection of Salmonella typhimurium led to tumor cell apoptosis and inhibited tumor angiogenesis. Additionally, Salmonella typhimurium treatment induced systemic antitumor immunity and reduced the growth of rechallenge tumors. Combination therapy of Salmonella typhimurium and PD-1 blockade showed enhanced suppression of schwannoma growth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Kang Liang, Rui Zhang, Haiyan Luo, Jinlong Zhang, Zhenyuan Tian, Xiaofen Zhang, Yulin Zhang, Md Kaisar Ali, Qingke Kong
Summary: In this study, different strains of S. Typhimurium were compared, with UK-1 (D) selected as the best candidate for further optimization. Through modification of lipid A structure, a new strain named D2 with stronger immunostimulatory activity was generated. In mouse models, engineered Salmonella bacteria equipped with anti-tumor molecules showed significant suppression of tumor growth and prolonged survival, demonstrating the potential of attenuated S. Typhimurium in delivering drug molecules with powerful anti-tumor activities.
FRONTIERS IN MICROBIOLOGY
(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.
Review
Biochemistry & Molecular Biology
Valentina Giansante, Gianmarco Stati, Silvia Sancilio, Emanuela Guerra, Saverio Alberti, Roberta Di Pietro, Joerg D. Hoheisel
Summary: Pancreatic cancer is the seventh leading cause of cancer-related death, and its incidence is increasing each year. The low relative survival rate and challenges of heterogeneity and tumor microenvironment in pancreatic cancer have emphasized the need for novel therapeutic strategies. This review focuses on the role of necroptosis in pancreatic cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
John P. Murad, Dileshni Tilakawardane, Anthony K. Park, Lupita S. Lopez, Cari A. Young, Jackson Gibson, Yukiko Yamaguchi, Hee Jun Lee, Kelly T. Kennewick, Brenna J. Gittins, Wen-Chung Chang, Chau P. Tran, Catalina Martinez, Anna M. Wu, Robert E. Reiter, Tanya B. Dorff, Stephen J. Forman, Saul J. Priceman
Summary: CAR T cell therapy has shown impressive clinical responses in hematological malignancies but limited effectiveness in solid tumors. Treatment with PSCA-CAR T cells for metastatic prostate and pancreas cancer requires cyclophosphamide preconditioning for efficacy, without observed toxicities in normal tissues expressing PSCA.
Article
Hematology
Zachary Davis, Martin Felices, Todd Lenvik, Sujan Badal, Joshua T. Walker, Peter Hinderlie, James L. Riley, Daniel A. Vallera, Bruce R. Blazar, Jeffrey S. Miller
Summary: The study showed that functional PD-1 is expressed on resting human NK cells in healthy individuals and reconstituting NK cells early after allo-HSCT. Blocking PD-1 on resting NK cells enhanced their function against PD-L1-expressing tumor lines, indicating the potential for PD-1 blockade in enhancing NK cell-mediated antitumor control.
Review
Biochemistry & Molecular Biology
Mehrdad Hefazi, Sara Bolivar-Wagers, Bruce R. Blazar
Summary: This review provides the latest preclinical and clinical data on Treg cell therapy in the context of GVHD, highlighting the importance of T cell therapy in preventing and treating GVHD, and discussing future research directions and challenges.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Darlene A. Monlish, Kevin J. Beezhold, Pailin Chiaranunt, Katelyn Paz, Nathan J. Moore, Andrea K. Dobbs, Rebecca A. Brown, John A. Ozolek, Bruce R. Blazar, Craig A. Byersdorfer
Summary: Research suggests that AMPK plays a significant role in alloreactive T cells posttransplant, with its absence lessening the severity of GVHD without compromising antileukemia responses or impairing immune reconstitution. This highlights potential for AMPK inhibition as an innovative approach to mitigate GVHD while preserving graft-versus-leukemia responses and maintaining robust immune reconstitution.
Review
Hematology
Zachariah DeFilipp, Mehrdad Hefazi, Yi-Bin Chen, Bruce R. Blazar
Summary: This article discusses the application of transplantation in the treatment of congenital or acquired nonmalignant blood diseases. Unlike patients with hematologic malignancies, the priority for nonmalignant blood disease patients is to avoid graft-versus-host disease, and emerging therapeutic methods hold promise for advancing transplantation care.
Article
Hematology
Rachael C. Adams, Dylan Carter-Cusack, Samreen N. Shaikh, Genesis T. Llanes, Rebecca L. Johnston, Gregory Quaife-Ryan, Glen Boyle, Lambros T. Koufariotis, Andreas Moller, Bruce R. Blazar, Jana Vukovic, Kelli P. A. MacDonald
Summary: This study reveals the development mechanism of chronic GVHD in the CNS after stem cell transplantation, including neuroinflammation and abnormal gene expression. The study found that donor-derived macrophages play an important role in CNS cGVHD.
Article
Biochemistry & Molecular Biology
Robert B. Levy, Hazem M. Mousa, Casey O. Lightbourn, Eric J. Shiuey, David Latoni, Stephanie Duffort, Ryan Flynn, Jing Du, Henry Barreras, Michael Zaiken, Katelyn Paz, Bruce R. Blazar, Victor L. Perez
Summary: Graft versus host disease (GVHD) is a complication of stem cell transplants, and ocular involvement occurs in a high percentage of patients. This study found a correlation between ocular and cutaneous involvement in chronic GVHD, suggesting shared immune mechanisms. Evaluating the ocular surface in patients with skin involvement may be valuable.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Vic Zamloot, Nancy Danielle Ebelt, Catherine Soo, Shweta Jinka, Edwin R. Manuel
Summary: Breast cancer often contains excessive stromal matrix components, such as hyaluronic acid (HA), which plays important roles in tumor progression and spread. This study shows that an attenuated Salmonella typhimurium secreting a bacterial hyaluronidase (YS-HAse) can degrade HA within murine breast tumors, resulting in enhanced tumor permeability and growth control. YS-HAse represents a promising new therapeutic approach that could be used alongside current treatments to improve their delivery and effectiveness.
Article
Hematology
Zachariah DeFilipp, Haesook T. Kim, Zhongming Yang, John Noonan, Bruce R. Blazar, Stephanie J. Lee, Steven Z. Pavletic, Corey Cutler
Summary: This study found that Belumosudil treatment was associated with lung-specific clinical responses in patients with BOS. Lung-specific responses were more commonly observed in patients with less advanced disease.
Article
Oncology
Nancy D. Ebelt, Edwin R. Manuel
Summary: Cancer cells can escape surveillance through epigenetic modifications, while hypomethylating agents (HMAs) have shown promise as a milder treatment option for leukemia patients. In this study, HMAs were tested on murine leukemias and found to re-establish immune-related gene expression, reduce leukemic burden, and improve survival. However, resistance and immune checkpoint protein expression were observed.
Article
Medicine, Research & Experimental
Gaelen K. Dwyer, Lisa R. Mathews, Jose A. Villegas, Anna Lucas, Anne Gonzalez de Peredo, Bruce R. Blazar, Jean-Philippe Girard, Amanda C. Poholek, Sanjiv A. Luther, Warren Shlomchik, Heth R. Turnquist
Summary: In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory antigen-presenting cells (APCs) secreting IL-12, which drives the response of donor Th1 cells, leading to graft-versus-host disease (GVHD). However, there are other mechanisms through which alloreactive T cell responses are initiated by directly acting on donor CD4(+) T cells. Among these mechanisms, fibroblastic reticular cell-derived DAMP IL-33 plays a critical role by enhancing T cell expansion and differentiation through the activation of T cell signaling pathways in response to alloantigen, resulting in GVHD.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Medicine, Research & Experimental
Gerard Socie, Leslie S. Kean, Robert Zeiser, Bruce R. Blazar
Summary: In the past 15 years, understanding of the pathophysiologic mechanisms underlying GVHD has significantly improved, but translation to clinical care has been slow and the clinical utility of new therapeutic agents has been inconsistent. New tools in immunology have recently been applied in the field of clinical GVHD, but there is a relative paucity of mechanistic insights into human translational research.
JOURNAL OF CLINICAL INVESTIGATION
(2021)