ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy

Veenstra, V.L. et al. (2018) ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy. Oncogenesis, 7, 87. (doi:10.1038/s41389-018-0096-9) (PMID:30442938) (PMCID:PMC6237826)

Veenstra, V.L. et al. (2018) ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy. Oncogenesis, 7, 87. (doi:10.1038/s41389-018-0096-9) (PMID:30442938) (PMCID:PMC6237826)

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.

Item Type:Articles
Additional Information:This work was supported by KWF Dutch Cancer Society (UVA 2012–5607 and UVA 2013–5932).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Biankin, Professor Andrew and Bailey, Dr Peter and Chang, Dr David
Authors: Veenstra, V.L., Damhofer, H., Waasdorp, C., van Rijssen, L.B., van de Vijver, M.J., Dijk, F., Wilmink, H.W., Besselink, M.G., Busch, O.R., Chang, D.K., Bailey, P.J., Biankin, A.V., Kocher, H.M., Medema, J.P., Li, J.S., Jiang, R., Pierce, D.W., van Laarhoven, H.W.M., and Bijlsma, M.F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogenesis
Publisher:Springer Nature
ISSN:2157-9024
ISSN (Online):2157-9024
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Oncogenesis 7: 87
Publisher Policy:Reproduced under a Creative Commons License

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