Anti-ASPSCR1 monoclonal antibody, clone 5B22B7H22

Sarcoma is a broad term for mesenchymal malignancies that arise from soft tissue or bone. Despite classification by histologic subtype, clinical behavior and response to therapy have great variability. Modern genetic sequencing techniques have been able to identify additional genetic variability and subsequently new targeted therapies. In this review, we discuss the current state of STS diagnostics and treatment and explore some of the more promising areas in which progress is being made. We discuss therapies targeting PDGFR alpha/KIT, beta-Catenin/APC/NOTCH, IDH-1/2 mutations, MDM2 amplifications, EZH2/INI1 expression loss, ALK fusion, and ASPSCR1-TFE3 fusion. We also discuss the progress that has been made within immunotherapies. While soft tissue sarcomas still portend a poor prognosis, these targeted therapies and immunotherapies provide treatment with less toxic side effects. (C) 2019 Elsevier Inc. All rights reserved.

PurposeNeoadjuvant chemotherapy studies have consistently reported a strong correlation between pathologic response and long-term outcome in triple-negative breast cancer (TNBC). We aimed to define minimal gene signatures for predicting chemoresponse by a three-step approach and to further develop a risk-stratification method of TNBC.MethodsThe first step involved the detection of genes associated with resistance to docetaxel in eight TNBC cell lines, leading to identification of thousands of candidate genes. Through subsequent second and third step analyses with gene set enrichment analysis and survival analysis using public expression profiles, the candidate gene list was reduced to prognostic core gene signatures comprising ten or four genes.ResultsThe prognostic core gene signatures include three up-regulated (CEBPD, MMP20, and WLS) and seven down-regulated genes (ASF1A, ASPSCR1, CHAF1B, DNMT1, GINS2, GOLGA2P5, and SKA1). We further develop a simple risk-stratification method based on expression profiles of the core genes. Relative expression values of the up-regulated and down-regulated core genes were averaged into two scores, Up and Down scores, respectively; then samples were stratified by a diagonal line in a xy plot of the Up and Down scores. Based on this method, the patients were successfully divided into subgroups with distinct chemoresponse and prognosis. The prognostic power of the method was validated in three independent public datasets containing 230, 141, and 117 TNBC patients with chemotherapy. In multivariable Cox regression analysis, the core gene signatures were significantly associated with prognosis independent of tumor stage and age at diagnosis. In meta-analysis, we found that five core genes (CEBPD, WLS, CHAF1B, GINS2, and SKA1) play opposing roles, either tumor promoter or suppressor, in TNBC and non-TNBC tumors respectively, depending on estrogen receptor status.ConclusionsThe results may provide a promising prognostic tool for predicting chemotherapy responders among TNBC patients prior to initiation of chemotherapeutic treatment.