Biomarkers for predicting the sensitivity of cancer cells to TRAIL-R1 agonistic monoclonal antibody.
Cancer letters 2010 Jan 5; In press
Araki S, Nakayama Y, Hori A, Yoshimura K
Pharmaceutical Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan.
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.