In 1905, the embryologist John Beard first proposed that pancreatic proteolytic enzymes had potential as a treatment for cancer. His theories were dismissed by the medical world a decade later, but various practitioners have kept the concept alive through the publication of case reports of cancer patients treated with pancreatic proteolytic enzymes. In the last 2 decades, studies of the role of proteases in physiology have made it clear that they do more than digest food. This article reviews the history of the clinical use of pancreatic proteolytic enzymes in cancer treatment, and recent research on protease activated receptors and their role in cancer.
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http://dx.doi.org/10.1177/15347354221096077 | DOI Listing |
Cells
January 2025
Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, 13353 Berlin, Germany.
Neuroendocrine neoplasms (NENs) are a diverse group originating from endocrine cells/their precursors in pancreas, small intestine, or lung. The key serum marker is chromogranin A (CgA). While commonly elevated in patients with NEN, its prognostic value is still under discussion.
View Article and Find Full Text PDFNat Commun
January 2025
Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
Cancers with activating mutations of KRAS show a high prevalence but remain intractable, requiring innovative strategies to overcome the poor targetability of KRAS. Here, we report that KRAS expression is post-translationally up-regulated through deubiquitination when the scaffolding function of NDRG3 (N-Myc downstream-regulated gene 3) promotes specific interaction between KRAS and a deubiquitinating enzyme, USP9X. In KRAS-mutant cancer cells KRAS protein expression, downstream signaling, and cell growth are highly dependent on NDRG3.
View Article and Find Full Text PDFHuman amylin, called also islet amyloid polypeptide (hIAPP), is the principal constituent of amyloid deposits in the pancreatic islets. Together with hyperglycemia, hIAPP-derived oligomers and aggregates are important culprits in type 2 diabetes mellitus (T2DM). Preventing aggregation, and in particular inhibiting the formation and/or stimulating degradation of toxic amylin oligomers formed early in the process, may reduce the negative effects of T2DM.
View Article and Find Full Text PDFJ Gastrointest Cancer
January 2025
Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Recent advances in targeted therapies have opened new avenues for intervention in PDAC, focusing on key genetic and molecular pathways that drive tumor progression.
Methods: In this review, we provide an overview on advances in novel targeted therapies in pancreatic adenocarcinoma.
Sci Rep
December 2024
CEDAR, Knight Cancer Institute, School of Medicine, Oregon Health and Science University, Portland, OR, 97201, USA.
Proteases are promising biomarkers for cancer early detection. Their enzymatic activity against peptide substrates allows for their straightforward detection using low-cost tests. However, the complexity of the human proteome makes it challenging to develop sensitive and selective tests against a specific protease biomarker.
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