Daniels Tracy R, Bernabeu Ezequiel, Rodríguez José A, Patel Shabnum, Kozman Maggie, Chiappetta Diego A, Holler Eggehard, Ljubimova Julia Y, Helguera Gustavo, Penichet Manuel L
Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Biochim Biophys Acta. 2012 Mar;1820(3):291-317. doi: 10.1016/j.bbagen.2011.07.016. Epub 2011 Aug 5.
Traditional cancer therapy can be successful in destroying tumors, but can also cause dangerous side effects. Therefore, many targeted therapies are in development. The transferrin receptor (TfR) functions in cellular iron uptake through its interaction with transferrin. This receptor is an attractive molecule for the targeted therapy of cancer since it is upregulated on the surface of many cancer types and is efficiently internalized. This receptor can be targeted in two ways: 1) for the delivery of therapeutic molecules into malignant cells or 2) to block the natural function of the receptor leading directly to cancer cell death.
In the present article we discuss the strategies used to target the TfR for the delivery of therapeutic agents into cancer cells. We provide a summary of the vast types of anti-cancer drugs that have been delivered into cancer cells employing a variety of receptor binding molecules including Tf, anti-TfR antibodies, or TfR-binding peptides alone or in combination with carrier molecules including nanoparticles and viruses.
Targeting the TfR has been shown to be effective in delivering many different therapeutic agents and causing cytotoxic effects in cancer cells in vitro and in vivo.
The extensive use of TfR for targeted therapy attests to the versatility of targeting this receptor for therapeutic purposes against malignant cells. More advances in this area are expected to further improve the therapeutic potential of targeting the TfR for cancer therapy leading to an increase in the number of clinical trials of molecules targeting this receptor. This article is part of a Special Issue entitled Transferrins: molecular mechanisms of iron transport and disorders.
传统的癌症治疗方法虽能成功摧毁肿瘤，但也会引发危险的副作用。因此，许多靶向治疗方法正在研发中。转铁蛋白受体（TfR）通过与转铁蛋白相互作用参与细胞对铁的摄取。该受体是癌症靶向治疗的一个有吸引力的分子，因为它在多种癌症类型的表面上调表达且能高效内化。该受体可通过两种方式进行靶向：1）用于将治疗分子递送至恶性细胞；2）阻断受体的天然功能，直接导致癌细胞死亡。
在本文中，我们讨论了将TfR作为靶点，将治疗药物递送至癌细胞的策略。我们总结了大量已通过多种受体结合分子（包括转铁蛋白、抗TfR抗体或TfR结合肽，单独或与包括纳米颗粒和病毒在内的载体分子联合使用）递送至癌细胞的抗癌药物类型。
已证明靶向TfR在体外和体内递送多种不同治疗药物并在癌细胞中产生细胞毒性作用方面是有效的。
TfR在靶向治疗中的广泛应用证明了将该受体作为靶点针对恶性细胞进行治疗的多功能性。预计该领域的更多进展将进一步提高靶向TfR进行癌症治疗的潜力，从而增加针对该受体的分子的临床试验数量。本文是名为“转铁蛋白：铁运输和疾病的分子机制”的特刊的一部分。
