Targeting the chemokine receptor CXCR4 for cancer therapies

Abstract 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...

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Main Authors: Ariana Rueda, Naroa Serna, Ramon Mangues, Antonio Villaverde, Ugutz Unzueta
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Biomarker Research
Subjects:
Online Access:https://doi.org/10.1186/s40364-025-00778-y
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author Ariana Rueda
Naroa Serna
Ramon Mangues
Antonio Villaverde
Ugutz Unzueta
author_facet Ariana Rueda
Naroa Serna
Ramon Mangues
Antonio Villaverde
Ugutz Unzueta
author_sort Ariana Rueda
collection DOAJ
description Abstract 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.
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series Biomarker Research
spelling doaj-art-9c0c0584d3f34ac5b0eb4375d06eb4192025-08-20T02:55:23ZengBMCBiomarker Research2050-77712025-05-0113112610.1186/s40364-025-00778-yTargeting the chemokine receptor CXCR4 for cancer therapiesAriana Rueda0Naroa Serna1Ramon Mangues2Antonio Villaverde3Ugutz Unzueta4Institut de Recerca Sant Pau (IR SANT PAU)CIBER de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos IIIInstitut de Recerca Sant Pau (IR SANT PAU)CIBER de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos IIIInstitut de Recerca Sant Pau (IR SANT PAU)Abstract 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.https://doi.org/10.1186/s40364-025-00778-yCXCR4Cancer Stem CellsBiotechnologyTargetingDrug deliveryTherapy
spellingShingle Ariana Rueda
Naroa Serna
Ramon Mangues
Antonio Villaverde
Ugutz Unzueta
Targeting the chemokine receptor CXCR4 for cancer therapies
Biomarker Research
CXCR4
Cancer Stem Cells
Biotechnology
Targeting
Drug delivery
Therapy
title Targeting the chemokine receptor CXCR4 for cancer therapies
title_full Targeting the chemokine receptor CXCR4 for cancer therapies
title_fullStr Targeting the chemokine receptor CXCR4 for cancer therapies
title_full_unstemmed Targeting the chemokine receptor CXCR4 for cancer therapies
title_short Targeting the chemokine receptor CXCR4 for cancer therapies
title_sort targeting the chemokine receptor cxcr4 for cancer therapies
topic CXCR4
Cancer Stem Cells
Biotechnology
Targeting
Drug delivery
Therapy
url https://doi.org/10.1186/s40364-025-00778-y
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