CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment. 2023

Shunshun Bao, and Mohammad Darvishi, and Ali H Amin, and Maysoon T Al-Haideri, and Indrajit Patra, and Khadisha Kashikova, and Irfan Ahmad, and Fahad Alsaikhan, and Zahraa Haleem Al-Qaim, and Moaed E Al-Gazally, and Bahman Abedi Kiasari, and Bahareh Tavakoli-Far, and Akmal A Sidikov, and Yasser Fakri Mustafa, and Reza Akhavan-Sigari
The First Clinical Medical College, Xuzhou Medical University, 221000, Xuzhou, China.

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.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D054377 Chemokine CXCL12 A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing. CXCL12 Chemokine,Stromal Cell-Derived Factor-1beta,Chemokine (C-X-C Motif) Ligand 12,Pre-B-Cell Growth-Stimulating Factor,SDF-1alpha,SDF-1beta,SDF1-3'A,Stromal Cell-Derived Factor 1,Stromal Cell-Derived Factor-1alpha,CXCL12, Chemokine,Cell-Derived Factor-1beta, Stromal,Chemokine, CXCL12,Growth-Stimulating Factor, Pre-B-Cell,Pre B Cell Growth Stimulating Factor,SDF 1alpha,SDF 1beta,SDF1 3'A,Stromal Cell Derived Factor 1,Stromal Cell Derived Factor 1alpha,Stromal Cell Derived Factor 1beta
D019718 Receptors, CXCR4 CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS. CXC Chemokine Receptor 4,CXCR4 Receptors,Fusin,CXCR4 Receptor,LESTR Receptor,Leukocyte-Derived Seven-Transmembrane Domain Receptor,Receptor, LESTR,Leukocyte Derived Seven Transmembrane Domain Receptor,Receptor, CXCR4
D063646 Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years. Tumorigenesis,Oncogenesis,Carcinogeneses,Oncogeneses,Tumorigeneses

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