Gemcitabine is still one of the standard
chemotherapy regimens for pancreatic ductal
adenocarcinoma (PDAC).
Gemcitabine uptake into
tumor cells is mainly through the human equilibrative
nucleoside transport 1 (hENT1). It was therefore proposed as a potential predictive
biomarker of
gemcitabine efficacy but reports are conflicting, with an important heterogeneity in methods to assess hENT1 expression. A multicenter cohort of 471 patients with a resected PDAC was used to assess simultaneously the predictive value of the 2 best described hENT1
antibodies (10D7G2 and SP120). Three additional
antibodies and the predictive value of hENT1
mRNA were also tested on 251 and 302 patients, respectively. hENT1 expression was assessed in 54 patients with matched primary
tumors and
metastases samples. The 10D7G2 clone was the only hENT1 antibody whose high expression was associated with a prolonged progression free survival and overall survival in patients who received adjuvant
gemcitabine. hENT1
mRNA level was also predictive of
gemcitabine benefit. hENT1 status was concordant in 83% of the cases with the best concordance in synchronous
metastases. The 10D7G2 clone has the best predictive value of
gemcitabine benefit in PDAC patients. Since it is not commercially available, hENT1
mRNA level could represent an alternative to assess hENT1 status.