Author/Authors :
Boeckx، نويسنده , , Carolien and Op de Beeck، نويسنده , , Ken and Wouters، نويسنده , , An and Deschoolmeester، نويسنده , , Vanessa and Limame، نويسنده , , Ridha and Zwaenepoel، نويسنده , , Karen and Specenier، نويسنده , , Pol and Pauwels، نويسنده , , Patrick and Vermorken، نويسنده , , Jan B. and Peeters، نويسنده , , Marc and Van Camp، نويسنده , , Guy and Baay، نويسنده , , Marc and Lardon، نويسنده , , Filip، نويسنده ,
Abstract :
Unraveling the underlying mechanisms of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) is of major importance as many tumors remain non-responsive or become resistant. Our microarray results suggest that “resistant” cells still exhibit RAS–MAPK pathway signaling contributing to drug resistance, as witnessed by low expression of DUSP5 and DUSP6, negative regulators of ERK1/2, and increased expression of AURKB, a key regulator of mitosis. Therefore, interrupting the RAS–MAPK pathway by an ERK1/2 inhibitor (apigenin) or an AURKB inhibitor (barasertib) might be a new strategy for overcoming cetuximab resistance in HNSCC.
Keywords :
Cetuximab resistance , Dual-specificity phosphatase 5 and 6 , Aurora kinase B , NanoPro 1000 , Anti-EGFR therapy , Head and neck squamous cell carcinoma
