TY - JOUR
T1 - TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer
AU - Salaun, Bruno
AU - Zitvogel, Laurence
AU - Asselin-Paturel, Carine
AU - Morel, Yannis
AU - Chemin, Karine
AU - Dubois, Clarisse
AU - Massacrier, Catherine
AU - Conforti, Rosa
AU - Chenard, Marie Pierre
AU - Sabourin, Jean Christophe
AU - Goubar, Aicha
AU - Lebecque, Serge
AU - Pierres, Michel
AU - Rimoldi, Donata
AU - Romero, Pedro
AU - Andre, Fabrice
PY - 2011/3/1
Y1 - 2011/3/1
N2 - The discovery of a targeted therapeutic compound along with its companion predictive biomarker is a major goal of clinical development for a personalized anticancer therapy to date. Here we present evidence of the predictive value of TLR3 expression by tumor cells for the efficacy of Poly (A:U) dsRNA in 194 breast cancer patients enrolled in a randomized clinical trial. Adjuvant treatment with double-stranded RNA (dsRNA) was associated with a significant decrease in the risk of metastatic relapse in TLR3 positive but not in TLR3-negative breast cancers. Moreover, we show the functional relevance of TLR3 expression by human tumor cells for the antitumor effects mediated by dsRNA in several preclinical mouse models carried out in immunocompromised animals. These 2 independent lines of evidence relied upon the generation of a novel tool, an anti-TLR3 antibody (40F9.6) validated for routine detection of TLR3 expression on paraffin-embedded tissues. Altogether, these data suggest that dsRNA mediates its therapeutic effect through TLR3 expressed on tumor cells, and could therefore represent an effective targeted treatment in patients with TLR3-positive cancers.
AB - The discovery of a targeted therapeutic compound along with its companion predictive biomarker is a major goal of clinical development for a personalized anticancer therapy to date. Here we present evidence of the predictive value of TLR3 expression by tumor cells for the efficacy of Poly (A:U) dsRNA in 194 breast cancer patients enrolled in a randomized clinical trial. Adjuvant treatment with double-stranded RNA (dsRNA) was associated with a significant decrease in the risk of metastatic relapse in TLR3 positive but not in TLR3-negative breast cancers. Moreover, we show the functional relevance of TLR3 expression by human tumor cells for the antitumor effects mediated by dsRNA in several preclinical mouse models carried out in immunocompromised animals. These 2 independent lines of evidence relied upon the generation of a novel tool, an anti-TLR3 antibody (40F9.6) validated for routine detection of TLR3 expression on paraffin-embedded tissues. Altogether, these data suggest that dsRNA mediates its therapeutic effect through TLR3 expressed on tumor cells, and could therefore represent an effective targeted treatment in patients with TLR3-positive cancers.
UR - http://www.scopus.com/inward/record.url?scp=79952212690&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-10-3490
DO - 10.1158/0008-5472.CAN-10-3490
M3 - Article
C2 - 21343393
AN - SCOPUS:79952212690
SN - 0008-5472
VL - 71
SP - 1607
EP - 1614
JO - Cancer Research
JF - Cancer Research
IS - 5
ER -