Biomarkers for predicting the sensitivity of cancer cells to TRAIL-R1 agonistic monoclonal antibody.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and an agonistic monoclonal antibody to TRAIL-R1 (TRAIL-R1 mAb) induce apoptosis and show anti-proliferative activity in vitro and in vivo. However, some TRAIL-R1-expressing cell lines are not sensitive to either TRAIL-R1 mAb or TRAIL. We have identified four genes (STK17B, SP140L, CASP8, and AIM1) whose expression levels differ significantly between TRAIL-R1 mAb-sensitive and resistant cell lines. Using the expression levels of these genes, we predicted TRAIL-R1 mAb and TRAIL sensitivity in our test cell lines with 75% (9/12) and 84% (21/25) accuracy, respectively. Knockdown of STK17B in TRAIL-R1 mAb-sensitive cells augmented Bcl-2 expression and suppressed TRAIL-R1 mAb-induced apoptosis. Our results may be useful for predicting the response of cancers to TRAIL-agonistic drugs in the clinic.
Araki
Shinsuke
S
Pharmaceutical Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan.
Nakayama
Yusuke
Y
Hori
Akira
A
Yoshimura
Koji
K
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015415:Biomarkers; D015153:Blotting, Western; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D016133:Polymerase Chain Reaction; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand