Overcoming the Fibrotic Fortress in Pancreatic Ductal Adenocarcinoma: Challenges and Opportunities

Min, Kay K Myo; Ffrench, Charlie B.; Jessup, Claire F.; Shepherdson, Mia; Barreto, Savio George; Bonder, Claudine S.

doi:10.3390/cancers15082354

Cited by 7 publications

(2 citation statements)

References 148 publications

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“…Pathological fibrosis is a characteristic of PC and considered a significant barrier to therapy effectiveness and immune recognition. 105 Based on recent advances, It became more obvious that the metabolic state of PDAC is highly unique and affects immune surveillance. 106 Recent research suggests a correlation between microbial diversity and PDAC outcome.…”

Section: Role Of Stroma In Supporting Tumor Immune Evasionmentioning

confidence: 99%

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment

Saleh,

Shihadeh,

Yousef

et al. 2024

Pancreas

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Background and Objectives Pancreatic cancer is one of the most lethal malignancies. Even though many substantial improvements in the survival rates for other major cancer forms were made, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Even more, no standard classification system for pancreatic cancer is based on cellular biomarkers. This review will discuss and provide updates about the role of stem cells in the progression of PC, the genetic changes associated with it, and the promising biomarkers for diagnosis. Materials and Methods The search process used PubMed, Cochrane Library, and Scopus databases to identify the relevant and related articles. Articles had to be published in English to be considered. Results The increasing number of studies in recent years has revealed that the diversity of cancer-associated fibroblasts is far greater than previously acknowledged, which highlights the need for further research to better understand the various cancer-associated fibroblast subpopulations. Despite the huge diversity in pancreatic cancer, some common features can be noted to be shared among patients. Mutations involving CDKN2, P53, and K-RAS can be seen in a big number of patients, for example. Similarly, some patterns of genes and biomarkers expression and the level of their expression can help in predicting cancer behavior such as metastasis and drug resistance. The current trend in cancer research, especially with the advancement in technology, is to sequence everything in hopes of finding disease-related mutations. Conclusion Optimizing pancreatic cancer treatment requires clear classification, understanding CAF roles, and exploring stroma reshaping approaches.

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Section: Role Of Stroma In Supporting Tumor Immune Evasionmentioning

confidence: 99%

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment

Saleh,

Shihadeh,

Yousef

et al. 2024

Pancreas

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“…At the stromal tissue level, the tumor environment is characterized by the continuous cross-talk between the immune system, cancer cells, several pro-inflammatory (such as, IL-1β, IL-2, IL-6, IL-17, and TNFα) and anti-inflammatory cytokines (such as TGFβ and IL-10) [38], chemokines, and chemokine ligands (such as chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 12 (CXCL12)) [39]. Moreover, the PDAC microenvironment is characterized by a low number of anti-tumor T-cells, and a high rate of M2 macrophages, MDSCs, and Tregs [40]. Furthermore, Tregs are activated by MDSCs in a cytokine-independent manner and induce the suppression of T-lymphocytes.…”

Section: Pdac Immunologymentioning

confidence: 99%

Pancreatic Ductal Adenocarcinoma and Nutrition: Exploring the Role of Diet and Gut Health

Gualtieri,

Cianci,

Frank

et al. 2023

Nutrients

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The incidence of pancreatic cancer is increasing worldwide. The most common form is represented by pancreatic ductal adenocarcinoma (PDAC) which has been shown to be linked to chronic inflammation. Notably, the gut microbiota has emerged as a critical player in regulating immune responses and inflammation. Indeed, intestinal dysbiosis, characterized by an imbalance in the gut microbiota composition, can contribute to the initiation of chronic inflammation. Sterile chronic inflammation can occur, probably activated by the translocation of bacterial components, such as lipopolysaccharide (LPS), the major component of Gram-negative microbiota, with the consequent induction of innate mucosal immunity, through the activation of Toll-like receptors (TLRs). Furthermore, the interaction between LPS and TLRs could enhance cancer progression. Recent research has shed light on the pivotal role of nutrition, as a modifiable risk factor, in PDAC immunological processes, particularly focusing on the immuno-modulatory effects of the gut microbiota. Different dietary regimens, fiber intake, immunonutrients, and antioxidants have the potential to either exacerbate or mitigate chronic inflammation, thereby influencing the pathogenesis and natural history of PDAC. These dietary components may affect the gut microbiota composition and, consequently, the level of inflammation, either promoting or protecting against PDAC. In this review of reviews, we discuss the modulatory role of nutrition and the gut microbiota in PDAC’s immunological processes to explore a translational therapeutic approach that could improve the survival and quality of life of these patients.

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Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics

Magrath,

Espinosa-Cotton,

Flinchum

et al. 2024

Front. Cell Dev. Biol.

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Desmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive pediatric cancer caused by a reciprocal translocation between chromosomes 11 and 22, leading to the formation of the EWSR1::WT1 oncoprotein. DSRCT presents most commonly in the abdominal and pelvic peritoneum and remains refractory to current treatment regimens which include chemotherapy, radiotherapy, and surgery. As a rare cancer, sample and model availability have been a limiting factor to DSRCT research. However, the establishment of rare tumor banks and novel cell lines have recently propelled critical advances in the understanding of DSRCT biology and the identification of potentially promising targeted therapeutics. Here we review model and dataset availability, current understanding of the EWSR1::WT1 oncogenic mechanism, and promising preclinical therapeutics, some of which are now advancing to clinical trials. We discuss efforts to inhibit critical dependencies including NTRK3, EGFR, and CDK4/6 as well as novel immunotherapy strategies targeting surface markers highly expressed in DSRCT such as B7-H3 or neopeptides either derived from or driven by the fusion oncoprotein. Finally, we discuss the prospect of combination therapies and strategies for prioritizing clinical translation.

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Overcoming the Fibrotic Fortress in Pancreatic Ductal Adenocarcinoma: Challenges and Opportunities

Cited by 7 publications

References 148 publications

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment

Pancreatic Ductal Adenocarcinoma and Nutrition: Exploring the Role of Diet and Gut Health

Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics

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