PRSS contributes to cetuximab resistance in colorectal cancer

Tan, Zhaoli; Gao, Lihua; Wang, Yan; Yin, Huihui; Xi, Yongyi; Wu, Xiaojie; Shao, Yong; Qiu, Weiyi; Du, Peng; Shen, Wenlong; Fu, Ling; Jia, Ru; Zhao, Chuanhua; Zhang, Yun; Zhao, Zhihu; Sun, Zhiwei; Chen, Hongxing; Hu, Xianwen; Xu, Jianming; Wang, Youliang

On the basis of the compelling in vitro evidence, we next assessed the therapeutic efficacy of SPINK1 combined with cetuximab treatment in a LoVo cell xenograft model. Treatment via cetuximab injection for 45 days significantly suppressed tumor growth (Fig. 5B) . Compared with either SPINK1 or cetuximab alone, the SPINK1 and cetuximab combination exhibited a clear synergistic effect (Fig. 5B) . Furthermore, combined treatment with SPINK1 and cetuximab resulted in a greater reduction in tumor weight than either SPINK1 or cetuximab treatment alone (Fig. 5C ). To determine whether any differences in EGFR/MEK signaling existed between cetuximab treatment alone and the SPINK1/cetuximab combination treatment in vivo, we measured pERK staining in xenograft tumor sections. The xenograft pERK levels were significantly decreased following treatment with cetuximab alone or with the combination of SPINK1 and cetuximab (Fig. 5D and fig. S6A ). Moreover, SPINK1 and cetuximab resulted in a greater reduction in the xenograft pERK levels than cetuximab alone (Fig. 5D and fig. S6A ).