Bringing DARC to Light: Role of Duffy Antigen/Receptor in Breast Cancer Progression and Cancer Prevention

Jha, Vaidehi; Talukdar, Joyeeta; Shankar, Abhishek; Ranjan, Piyush; Dhar, Ruby; Karmakar, Subhradip

doi:10.31557/APJCP.2025.26.10.3581

Bringing DARC to Light: Role of Duffy Antigen/Receptor in Breast Cancer Progression and Cancer Prevention

Document Type : Systematic Review and Meta-analysis

Authors

¹ Undergraduate Student, All India Institute of Medical Sciences, New Delhi, India.

² Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

³ Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.

⁴ Department of Surgery, All India Institute of Medical Sciences, New Delhi, India.

10.31557/APJCP.2025.26.10.3581

Abstract

Background: Duffy Antigen/Receptor for Chemokine (DARC), also called Atypical Chemokine Receptor 1 (ACKR1), is a seven-transmembrane receptor expressed on erythrocytes, lymphatic and vascular endothelial cells, keratinocytes, neurons, etc. ACKR1 is incapable of traditional G protein-coupling signaling and instead functions as a “decoy receptor,” binding multiple chemokines and facilitating their internalization and degradation. This regulates immune responses and inflammation, making it significant in the context of breast cancer. Methods: A comprehensive literature search was performed using keywords including “Duffy Antigen/Receptor for Chemokine (DARC)”, “Atypical Chemokine Receptor 1 (ACKR1)”, and “breast cancer”. Studies assessing ACKR1 expression in various breast cancer subtypes and its correlation with patient outcomes were analyzed. Results: Reduction in the levels of pro-angiogenic chemokines such as CCL2 can inhibit tumor growth, angiogenesis, and metastasis. High expression of ACKR1 is related to improved patient outcomes, such as enhanced disease-free survival. Conversely, low ACKR1 expression is associated with increased metastatic risk, especially in aggressive subtypes like triple-negative breast cancer. Conclusions: Given its potential as a biomarker and therapeutic target, further investigation into DARC’s mechanisms may reveal new strategies for cancer prevention and treatment. Overall, ACKR1 is a promising area of research, providing information about the interplay between inflammation, tumor progression, and immune surveillance.

Keywords

Main Subjects