%0 Journal Article
%T Breast Cancer, Chemokines, and Metastasis: A Search For Decoy Ligands of the CXCR4 Receptor - Breast Cancer, Chemokines, and Metastasis: A Search For Decoy Ligands of the CXCR4 Receptor - Open Access Pub
%A Gerald J. Mizejewski
%J OAP | Home | Journal of Neoplasms | Open Access Pub
%D 2018
%X Breast cancer (BC) is the leading cause of cancer-related deaths in young to middle-aged women worldwide. Moreover, the survival rate in BC-patients is only 20% when associated with metastatic disease. The high mortality rate observed in BC women with metastatic disease has precipitated a major challenge revealing an unmet need to develop new therapeutic strategies in treating metastatic cancer. One such approach has involved utilization of chemokines and their receptors as therapeutic targets for cancer metastasis. It has been established that a definitive correlation exists between overexpressed CXCR4 malignant cell receptors and cancer cell growth, invasion, and migration. It is also widely accepted that the CXCR4 receptor, complexed to its CXCL12 ligand, plays a major role in establishing migratory pathway gradients for cancer cells migrating to distant tissues/organ sites. It would follow that chemokine decoy ligands, such as peptide antagonists and inhibitors, could serve to induce receptor blockade and impede subsequent intracellular signaling. Such ligands, synthetic and natural, reportedly contribute to reducing cancer cell growth, invasion, adherence, and migration. The present commentary describes several existing synthetic CXCR4 receptor-ligand peptide antagonists and presents a strategy to develop naturally-occurring human protein-derived peptide candidates. DOI10.14302/issn.2639-1716.jn-18-2208 Breast cancer (BC) poses the highest incidence among cancer types in women and accounts for 30% of all new cancers in females worldwide 1. BC is also the leading cause of cancer-related deaths in women especially between ages of 20 to 50 years 2. When associated with extensive metastasis, BC-associated mortality rises to 80 - 90%. Hence, there exists major unmet needs in treating metastatic disease in BC patients, even though new chemo-therapeutic drugs are constantly being developed and assayed for efficacy. The survival rate in patients with BC metastatic disease approximates 20% of patients after 5 years 3. Thus, most cancer deaths can be attributed to metastasis rather than the primary tumor mass itself. The present commentary addresses this unmet need by discussing chemokine receptors and ligands as therapeutic targets for cancer growth and metastasis. Tumor cell metastasis appears to comprise five sequential steps as follows 2, 4. First, tumor cells shed from the primary tumor mass infiltrate and invade into local surrounding stromal cell extracellular matrix spaces and penetrate the basement membranes of nearby vasculature. Second, the
%U https://www.openaccesspub.org/jn/article/805