New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM.
Stefania ScalaCrescenzo D'AlterioSamantha MilanesiAlessandra CastagnaRoberta CarrieroFloriana Maria FarinaMassimo LocatiElena Monica BorroniPublished in: Vaccines (2020)
Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and spread. At present, different cancer types have been shown to overexpress C-X-C chemokine receptor type 4 (CXCR4) and to respond to its ligand C-X-C motif chemokine 12 (CXCL12). The CXCL12/CXCR4 axis influences cancer biology, promoting survival, proliferation, and angiogenesis, and plays a pivotal role in directing migration of cancer cells to sites of metastases, making it a prognostic marker and a therapeutic target. More recently, mutations in the C-terminus of CXCR4 have been identified in the genomic landscape of patients affected by Waldenstrom's macroglobulinemia, a rare B cell neoplasm. These mutations closely resemble those occurring in Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis (WHIM) syndrome, an immunodeficiency associated with CXCR4 aberrant expression and activity and with chemotherapy resistance in clinical trials. In this review, we summarize the current knowledge on the relevance of CXCR4 mutations in cancer biology, focusing on its importance as predictors of clinical presentation and response to therapy.
Keyphrases
- papillary thyroid
- clinical trial
- squamous cell
- cell migration
- endothelial cells
- healthcare
- poor prognosis
- end stage renal disease
- squamous cell carcinoma
- stem cells
- newly diagnosed
- induced apoptosis
- radiation therapy
- low grade
- chronic kidney disease
- young adults
- oxidative stress
- ejection fraction
- prognostic factors
- mesenchymal stem cells
- dna methylation
- peritoneal dialysis
- long non coding rna
- pi k akt
- cell cycle arrest
- network analysis