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OBJECTIVE While 67% of high grade serous ovarian cancers (HGSOC) express the estrogen receptor (ER), most fail antiestrogen therapy. Since mitogen-activated protein kinases (MAPK) activation is frequent in ovarian cancer, we investigated if estrogen regulates MAPK and if MEK inhibition (MEKi) reverses anti-estrogen resistance. METHODS Effects of MEKi (selumetinib), anti-estrogen (fulvestrant), or both were assayed in ER+ HGSOC in vitro and in xenografts. Response biomarkers were investigated by gene expression microarray and reverse phase protein array (RPPA). Genes differentially expressed in two independent primary HGSOCs datasets with high vs low pMAPK by RPPA were used to generate a “MAPK-activated gene signature”. Gene signature components reversed by MEKi were then identified. RESULTS High intratumor pMAPK independently predicts decreased survival (HR = 1.7, CI>95% 1.3–2.2, p=0.0009) in 408 TCGA HGSOC. A differentially expressed “MAPK-activated” gene subset was also prognostic. “MAPK-activated genes” in HGSOC differ from those in breast cancer. Combined MEK and ER blockade showed greater anti-tumor effects in xenografts than monotherapy. Gene set enrichment analysis and RPPA showed dual therapy downregulated DNA replication and cell cycle drivers, and upregulated lysosomal gene sets. Selumetinib reversed expression of a subset of “MAPK-activated genes” in vitro and/or in xenografts. Three of these genes were prognostic for poor survival (p=0.000265) and warrant testing as a signature predictive of MEKi response. CONCLUSION High pMAPK is independently prognostic and may underlie antiestrogen failure. Data support further evaluation of fulvestrant and selumetinib in ER+ HGSOC. The MAPK-activated HGSOC signature may help identify MEK inhibitor responsive tumors.

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PurposeThe purpose of this paper is to investigate the impact of buyer-seller interpersonal interactions on the purchase intention of buyers, incorporating swift guanxi as a mediator.Design/methodology/approachBased on survey data obtained from 336 Taobao Live users, PLS techniques were used to test hypotheses.FindingsSwift guanxi exists in buyer-seller interactions and matters, as it drives buyers' purchase intention in live stream shopping. Perceived expertise, perceived similarity and perceived likeability are found to be the three essential interpersonal interaction factors promoting the formation of swift guanxi. Perceived familiarity is also found to be significant but to a lesser extent. In addition, all these interpersonal interaction factors are found to significantly affect purchase intention through the mediation of swift guanxi.Originality/valueSwift guanxi has been less explored in live stream shopping. This study takes the lead in empirically examining the mediating role of swift guanxi in the relationship between interpersonal interaction factors and purchase intention and offers a description of key buyer-seller interpersonal interaction factors (perceived expertise, perceived similarity and perceived likeability), thereby helping to extend the swift guanxi literature in social commerce.