Neovascular Prostate-Specific Membrane Antigen Expression Is Associated with Improved Overall Survival under Palliative Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma

Stock, Katharina; Steinestel, Konrad; Wiesch, Rebekka; Mikesch, Jan‐Henrik; Hansmeier, Anna; Trautmann, Marcel; Beller, Nora; Rehkämper, Jan; Wardelmann, Eva; Heitkötter, Birthe; Hartmann, Wolfgang; Sperveslage, Jan; Huss, Sebastian

doi:10.1155/2017/2847303

Cited by 13 publications

(12 citation statements)

References 28 publications

(31 reference statements)

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“…This study also found that higher levels of PSMA expression correlated with higher pathological stages III and IV . Another German study detected PSMA in almost two‐thirds of the cases of pancreatic ductal adenocarcinoma associated neovasculature . However as with many other solid tumours, PSMA was only expressed in a small proportion of actual pancreatic adenocarcinoma cells .…”

Section: Introductionsupporting

confidence: 69%

“…Another German study detected PSMA in almost two‐thirds of the cases of pancreatic ductal adenocarcinoma associated neovasculature . However as with many other solid tumours, PSMA was only expressed in a small proportion of actual pancreatic adenocarcinoma cells . Further studies are needed to determine if these findings can be utilized in the early detection and treatment of pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

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Prostate‐specific membrane antigen for the surgical oncologist: interpreting expression beyond the prostate

Farag

Bolton

Lawrentschuk

2019

ANZ Journal of Surgery

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The use of prostate-specific membrane antigen (PSMA) radiotracer in positron emission tomography (PET) has been successfully incorporated into the clinical management of prostate cancer. However, PSMA tracer uptake is not limited to prostate cancer tissue. We reviewed studies exploring PSMA expression beyond the prostate gland using techniques of 68 Ga-PSMA PET imaging and immunohistochemistry. PSMA expression has been associated with a variety of solid tumours, and the vasculature associated with neoplastic disease, suggesting that this trans-membrane glycoprotein may be involved in the neovascularisation process in malignancy. These studies demonstrate the need for more research into the potential utility for 68 Ga-PSMA PET imaging in patients with non-prostatic cancers. © 2019 Royal Australasian College of Surgeons ANZ J Surg 90 (2020) 715-718ANZJSurg.com

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Section: Introductionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Prostate‐specific membrane antigen for the surgical oncologist: interpreting expression beyond the prostate

Farag

Bolton

Lawrentschuk

2019

ANZ Journal of Surgery

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“…The construction of PDAC TMAs has been described previously 71 . All tissue samples were collected for the purpose of histopathologic diagnosis and anonymised for the use in this study.…”

Section: Methodsmentioning

confidence: 99%

“…This was approved by the ethics committee of the University of Münster (Approval Number 2015-102-f-S). About 4 µM thick slides were cut and stained using anti-κB-Ras antibody (1:50 dilution) as previously described 71 . In brief, sections were deparaffinised in xylene and rehydrated through graded ethanol at room temperature.…”

Section: Methodsmentioning

confidence: 99%

κB-Ras and Ral GTPases regulate acinar to ductal metaplasia during pancreatic adenocarcinoma development and pancreatitis

Beel¹,

Kolloch²,

Apken³

et al. 2020

Nat Commun

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Pancreatic ductal adenocarcinoma (PDAC) is associated with high mortality and therapy resistance. Here, we show that low expression of κB-Ras GTPases is frequently detected in PDAC and correlates with higher histologic grade. In a model of KRas G12D-driven PDAC, loss of κB-Ras accelerates tumour development and shortens median survival. κB-Ras deficiency promotes acinar-to-ductal metaplasia (ADM) during tumour initiation as well as tumour progression through intrinsic effects on proliferation and invasion. κB-Ras proteins are also required for acinar regeneration after pancreatitis, demonstrating a general role in control of plasticity. Molecularly, upregulation of Ral GTPase activity and Sox9 expression underlies the observed phenotypes, identifying a previously unrecognized function of Ral signalling in ADM. Our results provide evidence for a tumour suppressive role of κB-Ras proteins and highlight low κB-Ras levels and consequent loss of Ral control as risk factors, thus emphasizing the necessity for therapeutic options that allow interference with Ral-driven signalling.

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“…Prostate-specific membrane antigen (PSMA) is a cell membrane-associated enzyme, functioning as carboxypeptidase, thereby degrading protein or peptide bonds. PSMA is believed to be involved in induction of tumor neoangiogenesis; however, the exact mechanism remains unclear [ 119 ]. PSMA is expressed in 68% of the tumor-associated neovasculature in PDAC, and to a lesser extent on tumor cells, while no PSMA overexpression in healthy pancreatic tissue and pancreatitis is reported [ 119 , 120 , 121 ].…”

Section: Molecular Targets In Pancreatic Ductal Adenocarcinoma (Pdac)mentioning

confidence: 99%

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Dam

Vuijk

Stibbe

et al. 2021

Cancers

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Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

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Neovascular Prostate-Specific Membrane Antigen Expression Is Associated with Improved Overall Survival under Palliative Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma

Cited by 13 publications

References 28 publications

Prostate‐specific membrane antigen for the surgical oncologist: interpreting expression beyond the prostate

Prostate‐specific membrane antigen for the surgical oncologist: interpreting expression beyond the prostate

κB-Ras and Ral GTPases regulate acinar to ductal metaplasia during pancreatic adenocarcinoma development and pancreatitis

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

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