Updated project metadata. High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). Using proteomics in ready-available HGSC tissues, we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data is able to predict patient response to first-line treatment (AUC: 0.82). Identification of chemoresistance at the time of diagnosis can facilitate the study of alternative treatments aimed at improving patient outcome. In addition, those patients classified as chemosensitive could undergo standard care with platinum-based agents. Therefore, the HGSC-1LTR strategy can allow optimization of therapeutic decision making and individualize HGSC patients’ care