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

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/ content/full/6/1/eaax5576/DC1 Fig. S1 . PRSS1 expression is significantly altered in colon cancer cells. Fig. S2 . Altering PRSS1 expression affected cetuximab inhibition of PI3K/AKT and MEK/ERK through cleavage of cetuximab, thus decreasing its effectiveness. Fig. S3 . PRSS1 cleaves cetuximab in a novel manner. Fig. S4 . Modified mAbs avoid PRSS1-mediated cleavage. Fig. S5 . SPINK1 effectively inhibits PRSS1 cleavage of mAbs. Fig. S6 . Cetuximab or bevacizumab combined with SPINK1 results in a synergistic reduction in colon cancer cell growth in vivo. Fig. S7 . Serum PRSS levels in patients with mCRC treated with chemotherapy before and after treatment with cetuximab. Fig. S8 . PRSS1 led to poor mAb effectiveness in cancer. Table S1 . Gene expression (PRSS1, PRSS2, and PRSS3) in a panel of cell lines (n = 49), including cell lines (n = 19) resistant to cetuximab and cell lines (n = 30) sensitive to cetuximab. Table S2 . Univariate and multivariate analyses of factors affecting PFS in patients who received cetuximab monotherapy. Data file S1A. The clinical information and test results of patients with mCRC treated with cetuximab. Data file S1B. The clinical information and test results of patients with mCRC treated with chemotherapy or other modalities. Data file S1C. The PRSS1 test results of the healthy controls.