Metastatic pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, with a 5-year survival rate of only 11%, necessitating identification of novel treatment paradigms. Tumor tissue specimens from patients with PDAC, breast cancer, and other solid tumor malignancies were collected and tumor cells were enriched using laser microdissection (LMD). Reverse phase protein array (RPPA) analysis was performed on enriched tumor cell lysates to quantify a 32-protein/phosphoprotein biomarker panel comprising known anticancer drug targets and/or cancer-related total and phosphorylated proteins, including HER2Total, HER2Y1248, and HER3Y1289. RPPA analysis revealed significant levels of HER2Total in PDAC patients at abundances comparable to HER2-positive (IHC 3+) and HER2-low (IHC 1+ /2+ , FISH−) breast cancer tissues, for which HER2 screening is routinely performed. These data support a critical unmet need for routine clinical evaluation of HER2 expression in PDAC patients and examination of the utility of HER2-directed antibody–drug conjugates in these patients.

中文翻译：

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PDAC 肿瘤中 HER2 蛋白表达的定量蛋白质组学分析

转移性胰腺癌 (PDAC) 是美国癌症相关死亡的第三大原因，其 5 年生存率仅为 11%，因此需要确定新的治疗模式。收集 PDAC、乳腺癌和其他实体瘤恶性肿瘤患者的肿瘤组织标本，并使用激光显微切割 (LMD) 富集肿瘤细胞。对富集的肿瘤细胞裂解物进行反相蛋白阵列 (RPPA) 分析，以量化包含已知抗癌药物靶点和/或癌症相关总蛋白和磷酸化蛋白（包括 HER2Total、HER2Y1248 和 HER3Y1289）的 32 蛋白/磷蛋白生物标志物组。RPPA 分析显示，PDAC 患者中 HER2Total 水平显着高于常规进行 HER2 筛查的 HER2 阳性 (IHC 3+) 和 HER2 低 (IHC 1+ /2+, FISH−) 乳腺癌组织。这些数据支持对 PDAC 患者 HER2 表达的常规临床评估以及检查 HER2 导向的抗体-药物偶联物在这些患者中的效用的关键未满足需求。