Persenaire Christianne, Bitler Benjamin G, Corr Bradley R
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Obstetrics & Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
medRxiv. 2024 Apr 14:2024.04.12.24305742. doi: 10.1101/2024.04.12.24305742.
Epithelial ovarian cancer (EOC) can be highly lethal, with limited therapeutic options for patients with non-homologous recombination deficient (HRD) disease. Folate receptor alpha (FOLR1/FRα)-targeting agents have shown promise both alone and in combination with available therapies, but the relationship of FRα to other treatment-driving biomarkers is unknown. The Cancer Genome Atlas (TCGA) was queried to assess protein and mRNA expression and mutational burden in patients with differential FRα protein-expressing ovarian tumors, and the results referenced against the standard 324 mutations currently tested through FoundationOne Companion Diagnostics to identify targets of interest. Of 585 samples within TCGA, 121 patients with serous ovarian tumors for whom FRα protein expression was quantified were identified. FRα protein expression significantly correlated with FOLR1 mRNA expression (p=7.19×10). Progression free survival (PFS) for the FRα-high group (Q1) was 20.7 months, compared to 16.6 months for the FRα-low group (Q4, Logrank, p=0.886). Overall survival (OS) was 54.1 months versus 36.3 months, respectively; however, this result was not significant (Q1 vs. Q4, Logrank, p=0.200). Mutations more commonly encountered in patients with high FRα-expressing tumors included PIK3CA and FGF family proteins. Combinations of FRα-targeting agents with PI3K, mTOR, FGF(R) and VEGF inhibitors warrant investigation to evaluate their therapeutic potential.
上皮性卵巢癌（EOC）可能具有高度致死性，对于非同源重组缺陷（HRD）疾病患者而言，治疗选择有限。靶向叶酸受体α（FOLR1/FRα）的药物已显示出单独使用以及与现有疗法联合使用的前景，但FRα与其他驱动治疗的生物标志物之间的关系尚不清楚。研究人员查询了癌症基因组图谱（TCGA），以评估FRα蛋白表达不同的卵巢肿瘤患者的蛋白质和mRNA表达以及突变负荷，并将结果与目前通过FoundationOne伴随诊断检测的标准324种突变进行对照，以确定感兴趣的靶点。在TCGA的585个样本中，识别出121例浆液性卵巢肿瘤患者，其FRα蛋白表达已被定量。FRα蛋白表达与FOLR1 mRNA表达显著相关（p=7.19×10）。FRα高表达组（Q1）的无进展生存期（PFS）为20.7个月，而FRα低表达组（Q4）为16.6个月（对数秩检验，p=0.886）。总生存期（OS）分别为54.1个月和36.3个月；然而，这一结果并不显著（Q1与Q4相比，对数秩检验，p=0.200）。在FRα高表达肿瘤患者中更常见的突变包括PIK3CA和FGF家族蛋白。靶向FRα的药物与PI3K、mTOR、FGF（R）和VEGF抑制剂的联合应用值得研究，以评估其治疗潜力。
