Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy.
Medical Oncology Unit, Azienda Ospedaliera San Paolo, Milan, Italy.
Target Oncol. 2018 Jun;13(3):333-351. doi: 10.1007/s11523-018-0567-0.
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors. In pancreatic cancer, mesothelin has been investigated mainly to address two unmet issues: the urgent need for new laboratory techniques for early tumor detection and the lack of successfully targetable oncogenic alterations for patients' treatment. In this review, we describe the clinicopathological significance of mesothelin expression in pancreatic cancer initiation and progression, we summarize available studies evaluating mesothelin as a potential diagnostic and prognostic biomarker in this disease, and we discuss current evidence and future perspectives of preclinical and clinical studies testing mesothelin as a molecular target for pancreatic cancer treatment.
间皮素是一种肿瘤分化抗原，在多种实体肿瘤中高度表达，包括胰腺癌。它在恶性细胞上的选择性表达和在有限数量的健康组织上的表达，使其成为作为诊断和预后生物标志物以及治疗靶点的研究的一个有趣候选物。基于强有力的临床前基础，许多针对间皮素的治疗药物已经进入临床试验，包括免疫毒素、单克隆抗体、抗体药物偶联物、癌症疫苗和嵌合抗原受体的过继 T 细胞疗法。在胰腺癌中，间皮素主要用于解决两个未满足的问题：对早期肿瘤检测的新实验室技术的迫切需求和缺乏可成功靶向的致癌改变以用于患者治疗。在这篇综述中，我们描述了间皮素在胰腺癌发生和进展中的临床病理意义，总结了评估间皮素作为该疾病潜在诊断和预后生物标志物的现有研究，并讨论了检测间皮素作为胰腺癌治疗的分子靶标进行的临床前和临床研究的现有证据和未来展望。
