First, tumor resistance limits efficacy: in glioblastoma (GBM), α5β1 suppresses p53 signaling to confer temozolomide resistance (Janouskova et al., 2012), and the β1 subunit activates DNA-repair and anti-apoptotic pathways, endowing cancer cells with chemoresistance—mechanisms likely operative in bone-metastatic cells as well (Eke et al., 2012; Dickreuter et al., 2016). Here, TP53 is linked to glioblastoma.