This was the case of resistant PC3 clones, with high levels of Notch1 and of Notch1-induced targets: CXCL6, already found overexpressed in bone-tropic phenotypes where skeletal colonization is favored [51], and EPAS1, a hypoxia-inducible factor that promotes tumorigenesis, angiogensis, and metastasis by direct interaction with the 8q24 prostate cancer locus [52]. Here, EPAS1 is linked to Familial prostate cancer.