Abstract 5169: Novel target molecules for treatment of cancer of unknown primary

Abstract

Abstract We have previously been involved in a multicenter clinical study to predict the primary site of cancer of unknown primary site (CUP) for a site-specific therapy. Based on the microarray analysis of gene expression pattern, we not only predicted the primary site for each CUP patient but also extracted 44 up-regulated genes common to each CUP showing over 2.5-fold change compared to normal tissue (lymph node). To identify genes related to CUP development among these candidate genes, we performed cell-based siRNA screening and estimated to what extend A549 cells reduce the ability of migration, and found 4 genes, GRN, MIF, PRKDC, PSMB4. Konckdown of each of these genes suppressed metastasis of implanted cells from a footpad to a popliteal lymph node. Inhibitors for PRKDC (NU 7441) and PSMB4 (bortezomib) also suppressed the metastasis of parental A549 cells in vivo, suggesting the involvement of these genes in metastasis. As there is no standard treatment for CUP, drugs targeting immune checkpoints, such as PD-1 or IDO, may reveal promising antitumor activity for CUP. Recent studies suggest that expression levels of PD-L1 (a PD-1's ligand) or IDO may be a biomarker of patient response to anti-PD-1 or anti-IDO therapy, respectively. We analyzed the expression of PD-L1 and IDO for the CUP tissues and found several patients with high expression of either or both proteins who may be most likely respond to these novel immunotherapies. Citation Format: Yoshihiko Fujita, Kazuko Sakai, Marco De Velasco, Takayasu Kurata, Hidetoshi Hayashi, Kazuhiko Nakagawa, Kazuto Nishio. Novel target molecules for treatment of cancer of unknown primary [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5169.