CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.

Shunshun Bao, Mohammad Darvishi, Ali H Amin, Maysoon T Al-Haideri, Indrajit Patra, Khadisha Kashikova, Irfan Ahmad, Fahad Alsaikhan, Zahraa Haleem Al-Qaim, Moaed E Al-Gazally, Bahman Abedi Kiasari, Bahareh Tavakoli-Far, Akmal A Sidikov, Yasser Fakri Mustafa, Reza Akhavan-Sigari

Journal: Journal of cancer research and clinical oncology 2023;149(10):7945-7968

PMID: 36905421

Abstract

CXC chemokine receptor type 4 (CXCR4) is a member of the G protein-coupled receptors (GPCRs) superfamily and is specific for CXC chemokine ligand 12 (CXCL12, also known as SDF-1), which makes CXCL12/CXCR4 axis. CXCR4 interacts with its ligand, triggering downstream signaling pathways that influence cell proliferation chemotaxis, migration, and gene expression. The interaction also regulates physiological processes, including hematopoiesis, organogenesis, and tissue repair. Multiple evidence revealed that CXCL12/CXCR4 axis is implicated in several pathways involved in carcinogenesis and plays a key role in tumor growth, survival, angiogenesis, metastasis, and therapeutic resistance. Several CXCR4-targeting compounds have been discovered and used for preclinical and clinical cancer therapy, most of which have shown promising anti-tumor activity. In this review, we summarized the physiological signaling of the CXCL12/CXCR4 axis and described the role of this axis in tumor progression, and focused on the potential therapeutic options and strategies to block CXCR4.

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Address: The First Clinical Medical College, Xuzhou Medical University, 221000, Xuzhou, China.; Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Department of Aerospace and Subaquatic Medicine, AJA University of Medicinal Sciences, Tehran, Iran.; Deanship of Scientific Research, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.; Zoology Department, Faculty of Science, Mansoura University, 35516, Mansoura, Egypt.; Department of Physiotherapy, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq.; An Independent Researcher, National Institute of Technology Durgapur, Durgapur, West Bengal, India.; Kazakh-Russian National Medical University, Almaty, Kazakhstan.; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.; College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.; Department of Anesthesia Techniques, Al-Mustaqbal University College, Hillah, Iraq.; College of Medicine, University of Al-Ameed, Karbala, Iraq.; Virology Department, Faculty of Veterinary Medicine, The University of Tehran, Tehran, Iran. [email protected].; Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran. [email protected].; Department of Physiology and Pharmacology, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Iran. [email protected].; Rector, Ferghana Medical Institute of Public Health, Ferghana, Uzbekistan.; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq.; Department of Neurosurgery, University Medical Center Tuebingen, Tübingen, Germany.; Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University, Warsaw, Poland.

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