These liabilities can be countered by adaptive pathways (CXCR7 compensation, STAT3 activation, stromal re-engagement), which tailored combinations, can counteract: chemo/RT (to take advantage of tumor-cell mobilization after transiting protective niches), ICI (to overcome antibodies’s immune homeostasis based on CXCR4), and anti-angiogenic/vascular-disrupting (to suppress CXCL12/CXCR4 rebound of therapy). This evidence concerns the gene CXCR4 and neoplasm.