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

To further confirm that PRSS1 decreases cetuximab efficacy and eventually leads to cetuximab resistance, we detected the PRSS1 level and pharmacokinetic profile of cetuximab in the serum of two patients with mCRC. One patient was very responsive to cetuximab, while the other was resistant to cetuximab. ELISA showed a significantly lower PRSS1 level in the patient with a good response than that in the other patient ( fig. S2G) , and immunoblotting showed a lower degree of cetuximab cleavage in the patient with a good response than that in the other patient ( fig. S2H ). Next, we detected the pharmacokinetics of cetuximab in the two patients using the goat antimouse IgG antibody and found a much lower cetuximab cleavage speed in the patient with a good response than in the other patient ( fig. S2I ), which further demonstrated that PRSS1 causes resistance to mAbs by cleaving mAbs.