Dataset Information

Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma.

ABSTRACT: BACKGROUND/AIMS: New imaging possibilities for early diagnosis of the devastating exocrine pancreatic adenocarcinomas would be highly welcome. Recently, pancreatic neuroendocrine tumours have been successfully visualised in vivo on the basis of their high density of receptors for the regulatory peptide somatostatin. Unfortunately, exocrine pancreatic tumours do not express sufficient amounts of somatostatin receptors. Therefore over-expression of other regulatory peptide receptors in these tumours needs to be found. METHODS: Receptors for the regulatory peptide neurotensin were evaluated in vitro by receptor autoradiography in 24 ductal pancreatic adenocarcinomas, 20 endocrine pancreatic cancers, 18 cases of chronic pancreatitis, and 10 normal pancreatic glands. RESULTS: Some 75% of all ductal pancreatic adenocarcinomas, most of them differentiated, were neurotensin receptor positive, whereas endocrine pancreatic cancers did not express neurotensin receptors. No neurotensin receptors were found in chronic pancreatitis or normal pancreatic tissues, including pancreatic acini, ducts, and islets. CONCLUSIONS: The selective and high expression of neurotensin receptors in ductal pancreatic adenocarcinomas could form the molecular basis for potential clinical applications, such as in vivo neurotensin receptor scintigraphy for early tumour diagnosis, radiotherapy with radiolabelled neurotensin analogues, and chemotherapy with neurotensin receptor antagonists.

SUBMITTER: Reubi JC

PROVIDER: S-EPMC1727058 | biostudies-other | 1998 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, with systemic therapy being the mainstay of treatment. Survival continues to be limited, typically less than 1 year. The PDAC microenvironment is characterized by a paucity of malignant epithelial cells, abundant stroma with predominantly immunosuppressive T cells and myelosuppressive-type macrophages (M2), and hypovascularity. The current treatment options for metastatic PDAC are modified (m)FOLFIRINOX /FOLFIRINOX or nab-paclitaxel and gemcitabine in patients with good performance status (PS) (ECOG 0-1/KPS 70-100%) and gemcitabine with or without a second agent for those with ECOG PS 2-3. New therapies are emerging, and the current guidelines endorse both germline and somatic testing in PDAC to evaluate actionable findings. Important themes related to new therapeutic approaches include DNA damage repair strategies, immunotherapy, targeting the stroma, and cancer-cell metabolism. Targeted therapy alone (outside small genomically defined subsets) or in combination with standard cytotoxic therapy, thus far, has proven disappointing in PDAC; however, novel therapies are evolving with increased integration of genomic profiling along with a better understanding of the tumor microenvironment and immunology. A small but important sub-group of patients have some of these agents available in the clinics for use. Olaparib was recently approved by the US Food and Drug Administration for maintenance therapy in germline BRCA1/2 mutated PDAC following demonstration of survival benefit in a phase 3 trial. Pembrolizumab is approved for patients with defects in mismatch repair/microsatellite instability. PDAC with wild-type KRAS represents a unique subgroup who have enrichment of potentially targetable oncogenic drivers. Small-molecule inhibitors including ERBB inhibitors (e.g., afatinib, MCLA-128), TRK inhibitors (e.g., larotrectinib, entrectinib), ALK/ROS inhibitor (e.g., crizotinib), and BRAF/MEK inhibitors are in development. In a small subset of patients with the KRASG12C mutation, a KRASG12C inhibitor, AMG510, and other agents are being investigated. Major efforts are underway to effectively target the tumor microenvironment and to integrate immunotherapy into the treatment of PDAC, and although thus far the impact has been modest to ineffective, nonetheless, there is optimism that some of the challenges will be overcome.

Dataset Information

Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure