Associated Genetic Biomarkers
Chemokine (C-X-C motif) receptor 4 (CXCR4) is a gene that encodes a protein that functions as a chemokine receptor that is specific for stromal cell-derived factor 1. The protein, along with the CD4 protein, supports HIV entry into cells. Missense mutations, nonsense mutations, silent mutations, and frameshift deletions are observed in cancers such as intestinal cancer, lung cancer, and skin cancer.
CXCR4 is altered in 0.79% of all cancers with prostate adenocarcinoma, lung adenocarcinoma, colon adenocarcinoma, cutaneous melanoma, and diffuse large B-cell lymphoma, not otherwise specified having the greatest prevalence of alterations .
The most common alterations in CXCR4 are CXCR4 Mutation (0.48%), CXCR4 Loss (0.28%), CXCR4 Nonsense (0.06%), CXCR4 R334* (0.02%), and CXCR4 Amplification (0.02%) .
CXCR4 status serves as an inclusion eligibility criteria in 5 clinical trials, of which 4 are open and 1 is closed. Of the trials that contain CXCR4 status as an inclusion criterion, 1 is phase 1 (1 open), 1 is phase 1/phase 2 (1 open), 1 is phase 2/phase 3 (0 open), and 2 are phase 3 (2 open).
Trials with CXCR4 status in the inclusion eligibility criteria most commonly target waldenstrom macroglobulinemia, acute lymphoblastic leukemia, and acute myeloid leukemia .
The most frequent alterations to serve as inclusion eligibility criteria are CXCR4 Mutation, CXCR4 Expression, CXCR4 S338*, and CXCR4 S338fs .
Ibrutinib, abatacept, carfilzomib, cytarabine, and daratumumab are the most frequent therapies in trials with CXCR4 as an inclusion criteria .
Significance of CXCR4 in Diseases
Waldenstrom Macroglobulinemia +
CXCR4 is an inclusion criterion in 3 clinical trials for waldenstrom macroglobulinemia, of which 3 are open and 0 are closed. Of the trials that contain CXCR4 status and waldenstrom macroglobulinemia as inclusion criteria, 1 is phase 1 (1 open), 1 is phase 1/phase 2 (1 open), and 1 is phase 3 (1 open) .
Acute Myeloid Leukemia +
Acute Lymphoblastic Leukemia +
CXCR4 is an inclusion criterion in 1 clinical trial for acute lymphoblastic leukemia, of which 1 is open and 0 are closed. Of the trial that contains CXCR4 status and acute lymphoblastic leukemia as inclusion criteria, 1 is phase 3 (1 open) .
Warts, Hypogammaglobulinemia, Infections, And Myelokathexis Syndrome (WHIMS) +
CXCR4 is an inclusion criterion in 1 clinical trial for warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIMS), of which 0 are open and 1 is closed. Of the trial that contains CXCR4 status and warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIMS) as inclusion criteria, 1 is phase 2/phase 3 (0 open) .
2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.
3. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.