CXCR4 and neoplasm: However, many in vitro studies have revealed that hypoxia can alter cell properties to directly contribute to tumor development, progression, and drug resistance through various mechanisms, such as up-regulation of MDR1 (drug resistance) [51], telomerase (cell immortality) [52,53], CXCR4 expression (cell migration and metastasis) [38], and down-regulation of the DNA repair system (genomic instability) [54].