Together with knowledge that endocytic dynamics are modulated by cancer (Schmid, 2017; Rosselli-Murai et al., 2018), further mechanistic investigations of how CME and clathrin-independent endocytosis regulate receptor biology is likely to reveal novel signaling mechanism that may provide new therapeutic strategies to selectively target pathogenic GPCR signaling such as CXCR4 in metastatic cancers. Here, CXCR4 is linked to metastatic malignant neoplasm.