Rueda Ariana, Serna Naroa, Mangues Ramon, Villaverde Antonio, Unzueta Ugutz
Institut de Recerca Sant Pau (IR SANT PAU), Sant Quintí 77 - 79, Barcelona, 08041, Spain.
CIBER de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, Madrid, 28029, Spain.
Biomark Res. 2025 May 1;13(1):68. doi: 10.1186/s40364-025-00778-y.
The C-X-C chemokine receptor type 4 (CXCR4) has emerged as a key molecular biomarker for cancer therapies due to its critical role in tumor progression and metastases by displaying a stem cells phenotype. Its overexpression has been observed in more than 20 types of cancers, including solid tumors and hematological malignancies, and it is often associated with tumor aggressiveness and poor prognosis. Being initially recognized as a co-receptor involved in HIV infection, numerous CXCR4-targeting ligands and antagonists, including small molecules, peptides and biologics have been identified over the past decades. While only few of them have been used in the context of cancer therapies, recent biotechnological advancements using CXCR4 as a molecular target are showing significant potential to revolutionize future cancer therapies. Therefore, this review highlights the biotechnological innovations developed for cancer therapy and diagnosis by targeting the chemokine receptor CXCR4. It also discusses future perspectives on emerging therapeutic strategies, ranging from the use of small molecule inhibitors that block receptor signaling to cutting-edge nanocarriers designed for the targeted delivery of innovative drugs and proteins into cancer stem cells, aiming at cell-selective precision nanomedicines.
C-X-C趋化因子受体4（CXCR4）已成为癌症治疗的关键分子生物标志物，因为它通过表现出干细胞表型在肿瘤进展和转移中起关键作用。在包括实体瘤和血液系统恶性肿瘤在内的20多种癌症中都观察到其过表达，并且它通常与肿瘤侵袭性和不良预后相关。CXCR4最初被认为是参与HIV感染的共受体，在过去几十年中，已经鉴定出许多靶向CXCR4的配体和拮抗剂，包括小分子、肽和生物制剂。虽然其中只有少数已用于癌症治疗，但最近以CXCR4为分子靶点的生物技术进展显示出在彻底改变未来癌症治疗方面的巨大潜力。因此，本综述重点介绍了通过靶向趋化因子受体CXCR4为癌症治疗和诊断开发的生物技术创新。它还讨论了新兴治疗策略的未来前景，从使用阻断受体信号传导的小分子抑制剂到设计用于将创新药物和蛋白质靶向递送至癌症干细胞的前沿纳米载体，目标是实现细胞选择性精准纳米药物。
