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

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.

• Authors: V L Veenstra, H Damhofer, C Waasdorp, L B van Rijssen, M J van de Vijver, F Dijk, H W Wilmink, M G Besselink, O R Busch, D K Chang, P J Bailey, A V Biankin, H M Kocher, J P Medema, J S Li, R Jiang, D W Pierce, H W M van Laarhoven, M F Bijlsma
• Journal: Oncogenesis (Oncogenesis) Vol. 7 Issue 11 Pg. 87 (Nov 16 2018) ISSN: 2157-9024 [Print] United States
• PMID: 30442938 (Publication Type: Journal Article)