Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
Lung Cancer. 2013 Apr;80(1):15-8. doi: 10.1016/j.lungcan.2012.12.021. Epub 2013 Jan 26.
Folate is essential for proliferating cells and folate transport pathways and folate-dependent metabolic processes show promise as targets for anti-neoplastic therapy. Folate receptor α (FOLR1), a folate transporter, is an attractive target for anti-neoplastic therapy due to its high affinity for folate, restricted range of expression in normal tissue and differential over-expression in malignant tissue. FOLR1 is expressed in non-small cell lung cancer, with a higher expression in adenocarcinoma compared with squamous cell carcinoma. Farletuzumab is a monoclonal antibody targeting FOLR1 which in pre-clinical studies led to cytotoxicity of FOLR1-expressing cells, inhibited tumor growth in animal models and showed limited reactivity with normal tissue. In phase I/II trials, farletuzumab was well tolerated as a single-agent and in combination, without additive toxicity with chemotherapy. An ongoing phase II, double blind, placebo-controlled study is evaluating farletuzumab in patients with FOLR1 expressing metastatic adenocarcinoma of lung.
叶酸对于增殖细胞和叶酸转运途径以及叶酸依赖的代谢过程至关重要，这些过程有望成为抗肿瘤治疗的靶点。叶酸受体α（FOLR1）是一种叶酸转运蛋白，由于其对叶酸具有高亲和力、在正常组织中的表达范围有限以及在恶性组织中的差异性过表达，因此成为抗肿瘤治疗的一个有吸引力的靶点。FOLR1 在非小细胞肺癌中表达，与鳞状细胞癌相比，腺癌中的表达更高。Farletuzumab 是一种针对 FOLR1 的单克隆抗体，在临床前研究中导致表达 FOLR1 的细胞的细胞毒性，抑制动物模型中的肿瘤生长，并与正常组织的反应有限。在 I/II 期试验中，farletuzumab 作为单一药物和联合用药具有良好的耐受性，与化疗无附加毒性。一项正在进行的 II 期、双盲、安慰剂对照研究正在评估 farletuzumab 在表达 FOLR1 的转移性肺腺癌患者中的疗效。
