Definition

A small molecular weight protein and an inhibitor of CXC chemokine receptor types 1 (CXCR1) and 2 (CXCR2), with potential immunomodulating, anti-inflammatory and antineoplastic activities. Upon administration, CXCR1/2 inhibitor RP72 targets and binds to CXCR1 and CXCR2 and prevents CXCR1 and CXCR2 activation by its ligand interleukin 8 (IL-8 or CXCL8). This blocks CXCL8-mediated signal transduction and may cause cancer stem cell (CSC) apoptosis. This may also reduce both recruitment and migration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and neutrophils in the tumor microenvironment (TME), inhibits inflammatory processes and abrogates the immunosuppressive-induced nature of the TME. This allows effector cells, such as natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), to kill and eliminate cancer cells. Altogether, blocking CXCL8-mediated signal transduction may inhibit tumor cell migration, metastasis, angiogenesis and tumor cell proliferation. CXCR1 and CXCR2, G protein-coupled receptors located on myeloid cells and certain tumor cells, play key roles in CSC survival and the ability of CSC to self-renew, the immunosuppressive nature of the TME, tumor cell proliferation and metastasis, and resistance to chemotherapeutic agents.